ClickCease
+1-915-850-0900 spinedoctors@gmail.com
Select Page

Cancer Health

Back Clinic Cancer Health Chiropractic Support Team. Abnormal growth of cells tends to proliferate uncontrollably and, in some cases, metastasize or (spread). As a result, cancer is one disease and a group of more than 100 different diseases. Cancer can involve any tissue of the body and have many different forms in each area. Most cancers are named after the cell or organ where they start. If a cancer spreads (metastasizes), the new tumor bears the same name as the original (primary) tumor.

Cancer is the Latin word for crab. The ancients used the word to mean a malignancy, doubtless because of the crab-like tenacity a malignant tumor sometimes seems to show grasping the tissues it invades. Cancer may also be called malignancy, a malignant tumor, or a neoplasm (literally, a new growth). The frequency of specific cancer may depend on gender.

For example, skin cancer is the most common type of malignancy for both men and women. The second common type in men is prostate cancer, and for women is breast cancer. Cancer frequency does not equate to cancer mortality. Skin cancers are curable. In comparison, lung cancer is the leading cause of death for both men and women in the United States today. Benign tumors are not cancer, and malignant tumors are cancer. Cancer is not contagious.

Cancer Health, In patients experience significant dynamic physical, psychosocial, and financial challenges. With the increasing number of patients with early-stage cancers transitioning to survivorship, there is a critical need to address health promotion and overall well-being.


Three Ways Cruciferous Vegetables Prevent Cancer El Paso, TX.

Three Ways Cruciferous Vegetables Prevent Cancer El Paso, TX.

Research has given us even more reasons to eat our veggies. Several studies have revealed that certain types of vegetables, specifically those known as cruciferous vegetables, have properties that could make them useful in preventing cancer.

What are Cruciferous Vegetables?

Some of the crunchiest, tastiest vegetables belong to the Cruciferae family. Typically cool weather vegetables, they are most notably characterized by four petal flowers somewhat resembling a cross.

These flower buds or the leaves are the parts of these plants that are most often consumed. However, the seeds or roots of some of these vegetables are also edible. Incorporating some of these cruciferous vegetables into your diet may help lower your risk for cancer:

  • Broccoli
  • Cabbage
  • Wasabi
  • Collard greens
  • Bok choi
  • Brussels sprout
  • Arugula
  • Cauliflower
  • Mustard (leaves and seeds)
  • Turnips
  • Horseradish
  • Rutabaga
  • Kale
  • Radish
  • Watercress

What is the Link Between Cruciferous Vegetables and Cancer?

Cruciferous vegetables are packed with nutrients that are believed to lower a person�s risk for several types of cancers, including prostate cancer, colorectal cancer, lung cancer, and breast cancer. This includes the carotenoids zeaxanthin, lutein, and beta-carotene as well as folate and vitamins C, E, and K. They are also rich in minerals and an excellent source of fiber which is well known for preventing colorectal cancer.

This group of vegetables is also a good dietary source of glucosinolates which also has cancer-fighting properties. When intact, the glucosinolates are not effective, but when they are broken down through chewing, processing, and pests, they then make contact with the myrosinase enzyme and initiate a process that releases specific chemicals that can prevent cancer.

cruciferous vegetables prevent cancer el paso tx.

How Cruciferous Vegetables Prevent Cancer

There are three primary ways that cruciferous vegetables can prevent cancer. Researchers have found substantial evidence that shows when they are part of a healthy, clean, low-fat diet, a person�s risk of cancer can be decreased.

  • Glucosinolates � These are chemicals that contain sulfur and are present in all cruciferous vegetables, giving them their trademark bitter flavor and pungent aroma. When this substance is broken down by chewing, preparation, or digestion, it forms certain compounds (indole-3-carbinol and sulforaphane) that scientists have identified as having �anticancer properties.� They do this by impeding the development or growth of cancer. Studies have looked at this effect on mice and rats and found that it is particularly useful in specific organs. Researchers are also looking at other ways the substances can prevent cancer. When working in the body, they:
    • Have anti-inflammatory properties
    • Aid in preventing DNA damage to cells
    • Inhibit the formation of blood vessels in tumors
    • Are antibacterial and antiviral
    • Inhibit the migration of tumor cells, thus halting metastasis
    • Cause cancerous cells to die
    • Aid in causing carcinogens to become inactiveBioactive components � Some studies have shown that the bioactive components of these veggies can affect the biomarkers of processes related to cancer in the human body such as decreasing abnormal cell growth. Genetic encoding of glutathione S-transferase � Glutathione S-transferase is an enzyme that helps the body metabolize and eliminate isothiocyanates. This is important because isothiocyanates prevent the activation of carcinogens, increase the speed at which the carcinogens are removed from the body, and counteract the dangerous effects of active carcinogens.

Best Ways to Consume Cruciferous Vegetables

Cruciferous vegetables are at their most nutritious and have the greatest cancer-fighting properties when they are raw. When the vegetables are chopped and chewed they release the most cancer-fighting chemicals. Likewise, when they are cooked, they lose a great deal of those properties. Steaming or cooking the vegetables very lightly for less than 5 minutes will allow them to retain some of those cancer-fighting properties.

So, make sure that you incorporate cruciferous vegetables into your diet at least three times a week. If you need further guidance, ask our doctor of chiropractic Dr. Jimenez. We’re here to help!

6 Day *DETOX DIET* Treatment | El Paso, TX (2019)

Nrf2 Explained: The Keap1-Nrf2 Pathway

Nrf2 Explained: The Keap1-Nrf2 Pathway

Oxidative stress is described as cell damage caused by free radicals, or unstable molecules, which can ultimately affect healthy function. The human body creates free radicals to neutralize bacteria and viruses, however, external factors, such as oxygen, pollution, and radiation, can often also produce free radicals. Oxidative stress has been associated with numerous health issues.

 

Oxidative stress and other stressors turn on internal protective mechanisms which can help regulate the human body’s antioxidant response. Nrf2 is a protein which senses levels of oxidative stress and enables the cells to protect themselves from internal and external factors. Nrf2 has also been demonstrated to help regulate genes involved in the production of antioxidant enzymes and stress-response genes. The purpose of the article below is to explain the effects of Nrf2 in cancer.

 

Abstract

 

The Keap1-Nrf2 pathway is the major regulator of cytoprotective responses to oxidative and electrophilic stress. Although cell signaling pathways triggered by the transcription factor Nrf2 prevent cancer initiation and progression in normal and premalignant tissues, in fully malignant cells Nrf2 activity provides growth advantage by increasing cancer chemoresistance and enhancing tumor cell growth. In this graphical review, we provide an overview of the Keap1-Nrf2 pathway and its dysregulation in cancer cells. We also briefly summarize the consequences of constitutive Nrf2 activation in cancer cells and how this can be exploited in cancer gene therapy.

 

Keywords: Nrf2, Keap1, Cancer, Antioxidant response element, Gene therapy

 

Introduction

 

The Keap1-Nrf2 pathway is the major regulator of cytoprotective responses to endogenous and exogenous stresses caused by reactive oxygen species (ROS) and electrophiles [1]. The key signaling proteins within the pathway are the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) that binds together with small Maf proteins to the antioxidant response element (ARE) in the regulatory regions of target genes, and Keap1 (Kelch ECH associating protein 1), a repressor protein that binds to Nrf2 and promotes its degradation by the ubiquitin proteasome pathway (Fig. 1). Keap1 is a very cysteine-rich protein, mouse Keap1 having a total of 25 and human 27 cysteine residues, most of which can be modified in vitro by different oxidants and electrophiles [2]. Three of these residues, C151, C273 and C288, have been shown to play a functional role by altering the conformation of Keap1 leading to nuclear translocation of Nrf2 and subsequent target gene expression [3] (Fig. 1). The exact mechanism whereby cysteine modifications in Keap1 lead to Nrf2 activation is not known, but the two prevailing but not mutually exclusive models are (1) the �hinge and latch� model, in which Keap1 modifications in thiol residues residing in the IVR of Keap1 disrupt the interaction with Nrf2 causing a misalignment of the lysine residues within Nrf2 that can no longer be polyubiquitinylated and (2) the model in which thiol modification causes dissociation of Cul3 from Keap1 [3]. In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs) (Fig. 2). In addition to modifications of Keap1 thiols resulting in Nrf2 target gene induction, proteins such as p21 and p62 can bind to Nrf2 or Keap1 thereby disrupting the interaction between Nrf2 and Keap1 [1], [3] (Fig. 3).

 

Fig. 1. Structures of Nrf2 and Keap1 and the cysteine code. (A) Nrf2 consists of 589 amino acids and has six evolutionarily highly conserved domains, Neh1-6. Neh1 contains a bZip motif, a basic region � leucine zipper (L-Zip) structure, where the basic region is responsible for DNA recognition and the L-Zip mediates dimerization with small Maf proteins. Neh6 functions as a degron to mediate degradation of Nrf2 in the nucleus. Neh4 and 5 are transactivation domains. Neh2 contains ETGE and DLG motifs, which are required for the interaction with Keap1, and a hydrophilic region of lysine residues (7 K), which are indispensable for the Keap1-dependent polyubiquitination and degradation of Nrf2. (B) Keap1 consists of 624 amino acid residues and has five domains. The two protein�protein interaction motifs, the BTB domain and the Kelch domain, are separated by the intervening region (IVR). The BTB domain together with the N-terminal portion of the IVR mediates homodimerization of Keap1 and binding with Cullin3 (Cul3). The Kelch domain and the C-terminal region mediate the interaction with Neh2. (C) Nrf2 interacts with two molecules of Keap1 through its Neh2 ETGE and DLG motifs. Both ETGE and DLG bind to similar sites on the bottom surface of the Keap1 Kelch motif. (D) Keap1 is rich in cysteine residues, with 27 cysteines in human protein. Some of these cysteines are located near basic residues and are therefore excellent targets of electrophiles and oxidants. The modification pattern of the cysteine residues by electrophiles is known as the cysteine code. The cysteine code hypothesis proposes that structurally different Nrf2 activating agents affect different Keap1 cysteines. The cysteine modifications lead to conformational changes in the Keap1 disrupting the interaction between the Nrf2 DLG and Keap1 Kelch domains, thus inhibiting the polyubiquitination of Nrf2. The functional importance of Cys151, Cys273 and Cys288 has been shown, as Cys273 and Cys288 are required for suppression of Nrf2 and Cys151 for activation of Nrf2 by inducers [1], [3].

 

Fig. 2. The Nrf2-Keap1 signaling pathway. (A and B) in basal conditions, two Keap1 molecules bind to Nrf2 and Nrf2 is polyubiquitylated by the Cul3-based E3 ligase complex. This polyubiquitilation results in rapid Nrf2 degradation by the proteasome. A small proportion of Nrf2 escapes the inhibitory complex and accumulates in the nucleus to mediate basal ARE-dependent gene expression, thereby maintaining the cellular homeostasis. (C) Under stress conditions, inducers modify the Keap1 cysteines leading to the inhibition of Nrf2 ubiquitylation via dissociation of the inhibitory complex. (D) According to the hinge and latch model, modification of specific Keap1 cysteine residues leads to conformational changes in Keap1 resulting in the detachment of the Nrf2 DLG motif from Keap1. Ubiquitination of Nrf2 is disrupted but the binding with the ETGE motif remains. (E) In the Keap1-Cul3 dissociation model, the binding of Keap1 and Cul3 is disrupted in response to electrophiles, leading to the escape of Nrf2 from the ubiquitination system. In both of the suggested models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the Antioxidant Response Element (ARE) and drive the expression of Nrf2 target genes such as NQO1, HMOX1, GCL and GSTs [1], [3].

 

Fig. 3. Mechanisms for constitutive nuclear accumulation of Nrf2 in cancer. (A) Somatic mutations in Nrf2 or Keap1 disrupt the interaction of these two proteins. In Nrf2, mutations affect ETGE and DLG motifs, but in Keap1 mutations are more evenly distributed. Furthermore, oncogene activation, such as KrasG12D[5], or disruption of tumor suppressors, such as PTEN [11] can lead to transcriptional induction of Nrf2 and an increase in nuclear Nrf2. (B) Hypermethylation of the Keap1 promoter in lung and prostate cancer leads to reduction of Keap1 mRNA expression, which increases the nuclear accumulation of Nrf2 [6], [7]. (C) In familial papillary renal carcinoma, the loss of fumarate hydratase enzyme activity leads to the accumulation of fumarate and further to succination of Keap1 cysteine residues (2SC). This post-translational modification leads to the disruption of Keap1-Nrf2 interaction and nuclear accumulation of Nrf2 [8], [9]. (D) Accumulation of disruptor proteins such as p62 and p21 can disturb Nrf2-Keap1 binding and results in an increase in nuclear Nrf2. p62 binds to Keap1 overlapping the binding pocket for Nrf2 and p21 directly interacts with the DLG and ETGE motifs of Nrf2, thereby competing with Keap1 [10].

 

Mechanisms of Activation and Dysregulation of Nrf2 in Cancer

 

Although cytoprotection provided by Nrf2 activation is important for cancer chemoprevention in normal and premalignant tissues, in fully malignant cells Nrf2 activity provides growth advantage by increasing cancer chemoresistance and enhancing tumor cell growth [4]. Several mechanisms by which Nrf2 signaling pathway is constitutively activated in various cancers have been described: (1) somatic mutations in Keap1 or the Keap1 binding domain of Nrf2 disrupting their interaction; (2) epigenetic silencing of Keap1 expression leading to defective repression of Nrf2; (3) accumulation of disruptor proteins such as p62 leading to dissociation of the Keap1-Nrf2 complex; (4) transcriptional induction of Nrf2 by oncogenic K-Ras, B-Raf and c-Myc; and (5) post-translational modification of Keap1 cysteines by succinylation that occurs in familial papillary renal carcinoma due to the loss of fumarate hydratase enzyme activity [3], [4], [5], [6], [7], [8], [9], [10] (Fig. 3). Constitutively abundant Nrf2 protein causes increased expression of genes involved in drug metabolism thereby increasing the resistance to chemotherapeutic drugs and radiotherapy. In addition, high Nrf2 protein level is associated with poor prognosis in cancer [4]. Overactive Nrf2 also affects cell proliferation by directing glucose and glutamine towards anabolic pathways augmenting purine synthesis and influencing the pentose phosphate pathway to promote cell proliferation [11] (Fig. 4).

 

Fig. 4. The dual role of Nrf2 in tumorigenesis. Under physiological conditions, low levels of nuclear Nrf2 are sufficient for the maintenance of cellular homeostasis. Nrf2 inhibits tumor initiation and cancer metastasis by eliminating carcinogens, ROS and other DNA-damaging agents. During tumorigenesis, accumulating DNA damage leads to constitutive hyperactivity of Nrf2 which helps the autonomous malignant cells to endure high levels of endogenous ROS and to avoid apoptosis. Persistently elevated nuclear Nrf2 levels activate metabolic genes in addition to the cytoprotective genes contributing to metabolic reprogramming and enhanced cell proliferation. Cancers with high Nrf2 levels are associated with poor prognosis because of radio and chemoresistance and aggressive cancer cell proliferation. Thus, Nrf2 pathway activity is protective in the early stages of tumorigenesis, but detrimental in the later stages. Therefore, for the prevention of cancer, enhancing Nrf2 activity remains an important approach whereas for the treatment of cancer, Nrf2 inhibition is desirable [4], [11].

 

Given that high Nrf2 activity commonly occurs in cancer cells with adverse outcomes, there is a need for therapies to inhibit Nrf2. Unfortunately, due to structural similarity with some other bZip family members, the development of specific Nrf2 inhibitors is a challenging task and only a few studies of Nrf2 inhibition have been published to date. By screening natural products, Ren et al. [12] identified an antineoplastic compound brusatol as an Nrf2 inhibitor that enhances the chemotherapeutic efficacy of cisplatin. In addition, PI3K inhibitors [11], [13] and Nrf2 siRNA [14] have been used to inhibit Nrf2 in cancer cells. Recently, we have utilized an alternative approach, known as cancer suicide gene therapy, to target cancer cells with high Nrf2 levels. Nrf2-driven lentiviral vectors [15] containing thymidine kinase (TK) are transferred into cancer cells with high ARE activity and the cells are treated with a pro-drug, ganciclovir (GCV). GCV is metabolized to GCV-monophosphate, which is further phosphorylated by cellular kinases into a toxic triphosphate form [16] (Fig. 5). This leads to effective killing of not only TK containing tumor cells, but also the neighboring cells due to the bystander effect [17]. ARE-regulated TK/GCV gene therapy can be further enhanced via combining a cancer chemotherapeutic agent doxorubicin to the treatment [16], supporting the notion that this approach could be useful in conjuction with traditional therapies.

 

Fig. 5. Suicide gene therapy. Constitutive Nrf2 nuclear accumulation in cancer cells can be exploited by using Nrf2-driven viral vector for cancer suicide gene therapy [16]. In this approach, lentiviral vector (LV) expressing thymidine kinase (TK) under minimal SV40 promoter with four AREs is transduced to lung adenocarcinoma cells. High nuclear Nrf2 levels lead to robust expression of TK through Nrf2 binding. Cells are then treated with a pro-drug, ganciclovir (GCV), which is phosphorylated by TK. Triphosphorylated GCV disrupts DNA synthesis and leads to effective killing of not only TK containing tumor cells, but also the neighboring cells due to the bystander effect.

 

Dr Jimenez White Coat

Nrf2 is a master regulator which triggers the production of powerful antioxidants in the human body which help eliminate oxidative stress. Various antioxidant enzymes, such as superoxide dismutase, or SOD, glutathione, and catalase, are also activated through the Nrf2 pathway. Furthermore, certain phytochemicals like turmeric, ashwagandha, bacopa, green tea, and milk thistle, activate Nrf2. Research studies have found that Nrf2 activation can naturally enhance cellular protection and restore balance to the human body.

Dr. Alex Jimenez D.C., C.C.S.T. Insight

 

Sulforaphane and Its Effects on Cancer, Mortality, Aging, Brain and Behavior, Heart Disease & More

 

Isothiocyanates are some of the most important plant compounds you can get in your diet. In this video I make the most comprehensive case for them that has ever been made. Short attention span? Skip to your favorite topic by clicking one of the time points below. Full timeline below.

 

Key sections:

 

  • 00:01:14 – Cancer and mortality
  • 00:19:04 – Aging
  • 00:26:30 – Brain and behavior
  • 00:38:06 – Final recap
  • 00:40:27 – Dose

 

Full timeline:

 

  • 00:00:34 – Introduction of sulforaphane, a major focus of the video.
  • 00:01:14 – Cruciferous vegetable consumption and reductions in all-cause mortality.
  • 00:02:12 – Prostate cancer risk.
  • 00:02:23 – Bladder cancer risk.
  • 00:02:34 – Lung cancer in smokers risk.
  • 00:02:48 – Breast cancer risk.
  • 00:03:13 – Hypothetical: what if you already have cancer? (interventional)
  • 00:03:35 – Plausible mechanism driving the cancer and mortality associative data.
  • 00:04:38 – Sulforaphane and cancer.
  • 00:05:32 – Animal evidence showing strong effect of broccoli sprout extract on bladder tumor development in rats.
  • 00:06:06 – Effect of direct supplementation of sulforaphane in prostate cancer patients.
  • 00:07:09 – Bioaccumulation of isothiocyanate metabolites in actual breast tissue.
  • 00:08:32 – Inhibition of breast cancer stem cells.
  • 00:08:53 – History lesson: brassicas were established as having health properties even in ancient Rome.
  • 00:09:16 – Sulforaphane’s ability to enhance carcinogen excretion (benzene, acrolein).
  • 00:09:51 – NRF2 as a genetic switch via antioxidant response elements.
  • 00:10:10 – How NRF2 activation enhances carcinogen excretion via glutathione-S-conjugates.
  • 00:10:34 – Brussels sprouts increase glutathione-S-transferase and reduce DNA damage.
  • 00:11:20 – Broccoli sprout drink increases benzene excretion by 61%.
  • 00:13:31 – Broccoli sprout homogenate increases antioxidant enzymes in the upper airway.
  • 00:15:45 – Cruciferous vegetable consumption and heart disease mortality.
  • 00:16:55 – Broccoli sprout powder improves blood lipids and overall heart disease risk in type 2 diabetics.
  • 00:19:04 – Beginning of aging section.
  • 00:19:21 – Sulforaphane-enriched diet enhances lifespan of beetles from 15 to 30% (in certain conditions).
  • 00:20:34 – Importance of low inflammation for longevity.
  • 00:22:05 – Cruciferous vegetables and broccoli sprout powder seem to reduce a wide variety of inflammatory markers in humans.
  • 00:23:40 – Mid-video recap: cancer, aging sections
  • 00:24:14 – Mouse studies suggest sulforaphane might improve adaptive immune function in old age.
  • 00:25:18 – Sulforaphane improved hair growth in a mouse model of balding. Picture at 00:26:10.
  • 00:26:30 – Beginning of brain and behavior section.
  • 00:27:18 – Effect of broccoli sprout extract on autism.
  • 00:27:48 – Effect of glucoraphanin on schizophrenia.
  • 00:28:17 – Start of depression discussion (plausible mechanism and studies).
  • 00:31:21 – Mouse study using 10 different models of stress-induced depression show sulforaphane similarly effective as fluoxetine (prozac).
  • 00:32:00 – Study shows direct ingestion of glucoraphanin in mice is similarly effective at preventing depression from social defeat stress model.
  • 00:33:01 – Beginning of neurodegeneration section.
  • 00:33:30 – Sulforaphane and Alzheimer’s disease.
  • 00:33:44 – Sulforaphane and Parkinson’s disease.
  • 00:33:51 – Sulforaphane and Hungtington’s disease.
  • 00:34:13 – Sulforaphane increases heat shock proteins.
  • 00:34:43 – Beginning of traumatic brain injury section.
  • 00:35:01 – Sulforaphane injected immediately after TBI improves memory (mouse study).
  • 00:35:55 – Sulforaphane and neuronal plasticity.
  • 00:36:32 – Sulforaphane improves learning in model of type II diabetes in mice.
  • 00:37:19 – Sulforaphane and duchenne muscular dystrophy.
  • 00:37:44 – Myostatin inhibition in muscle satellite cells (in vitro).
  • 00:38:06 – Late-video recap: mortality and cancer, DNA damage, oxidative stress and inflammation, benzene excretion, cardiovascular disease, type II diabetes, effects on the brain (depression, autism, schizophrenia, neurodegeneration), NRF2 pathway.
  • 00:40:27 – Thoughts on figuring out a dose of broccoli sprouts or sulforaphane.
  • 00:41:01 – Anecdotes on sprouting at home.
  • 00:43:14 – On cooking temperatures and sulforaphane activity.
  • 00:43:45 – Gut bacteria conversion of sulforaphane from glucoraphanin.
  • 00:44:24 – Supplements work better when combined with active myrosinase from vegetables.
  • 00:44:56 – Cooking techniques and cruciferous vegetables.
  • 00:46:06 – Isothiocyanates as goitrogens.

 

Acknowledgments

 

This work was supported by the Academy of Finland, the Sigrid Juselius Foundation and the Finnish Cancer Organisations.

 

In conclusion, nuclear factor (erythroid-derived 2)-like 2, also known as NFE2L2 or Nrf2, is a protein which increases the production of antioxidants which protect the human body against oxidative stress. As described above, the stimulation of the Nrf2 pathway are being studies for the treatment of diseases caused by oxidative stress, including cancer. The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at�915-850-0900�.

 

Curated by Dr. Alex Jimenez

 

Referenced from:�Sciencedirect.com

 

Green Call Now Button H .png

 

Additional Topic Discussion: Relieving Knee Pain without Surgery

 

Knee pain is a well-known symptom which can occur due to a variety of knee injuries and/or conditions, including�sports injuries. The knee is one of the most complex joints in the human body as it is made-up of the intersection of four bones, four ligaments, various tendons, two menisci, and cartilage. According to the American Academy of Family Physicians, the most common causes of knee pain include patellar subluxation, patellar tendinitis or jumper’s knee, and Osgood-Schlatter disease. Although knee pain is most likely to occur in people over 60 years old, knee pain can also occur in children and adolescents. Knee pain can be treated at home following the RICE methods, however, severe knee injuries may require immediate medical attention, including chiropractic care.

 

 

blog picture of cartoon paper boy

 

EXTRA EXTRA | IMPORTANT TOPIC: Recommended El Paso, TX Chiropractor

 

***

How Chiropractic Can Be Used As Supportive Care For Cancer

How Chiropractic Can Be Used As Supportive Care For Cancer

Cancer puts a tremendous amount of stress on the body. Cancer treatments add to that stress, affecting the organs as well as the musculoskeletal system. Pain is a common complaint among cancer patients. They experience a variety of aches and pains including headaches, neck pain, muscle tension, and back pain as well as painful peripheral neuropathy. They may also have mobility problems and difficulty walking.

Many cancer patients have found chiropractic care to be a very effective treatment for pain management and to improve flexibility, mobility, and muscle strength. They find it helps to reduce stress and helps the body function more efficiently.

It provides these benefits without the use of medication or invasive treatments. For patients undergoing chemotherapy, it is very beneficial because chiropractic�s whole body approach to wellness helps to combat the debilitating effects of the treatment.

Benefits of Chiropractic Care for Cancer Patients

There are many different reasons that cancer patients may seek chiropractic treatment. Cancer is, in itself, very hard on the body. The disease can cause headaches, muscle stiffness, neck pain, and back pain. However, the treatments can also cause problems.

Patients undergoing radiation treatment must lie on a table for extended periods of time which can be very uncomfortable. Surgery can cause pain in the joints and connective tissues. Chemotherapy drugs can cause unpleasant side effects including nausea, neuropathy, and headaches.

Some of the ways chiropractic care can help cancer patients include:

  • The relief of nausea, headaches, and fatigue
  • Improved balance
  • Alleviation of neck and back pain and stiffness
  • Reduction of joint inflammation
  • Better mobility
  • Restoration of nerve function
  • Reduced muscle tension

Often cancer patients have also reported improvements beyond the typical musculoskeletal complaints that chiropractic treats. Reduced effects of peripheral neuropathy, improved digestion, and even easier respiratory function are just some of the added benefits.

cancer chiropractic support el paso tx.

Chiropractic Treatment Approaches

Chiropractors use a drug-free, hands-on approach to treatment for a wide range of issues. It restores nerve function, corrects musculoskeletal problems, and helps to bring the body back into proper alignment. It is non-invasive and offers patients a safe, natural alternative to medications and other treatments that can have unwanted side effects.

One barrier that may prevent a patient from seeking chiropractic care is the common misconception that it is aggressive and forceful, even painful. The truth is, most chiropractic techniques are very gentle, applying very low force and some no force at all.

Most are also not painful at all and work quickly to enhance the range of motion and increase energy as well as reduce pain. It can help relieve a patient�s symptoms while helping them stay strong while they undergo treatment.

Some of the chiropractic treatment options that are used for cancer patients include:

  • Spinal manipulation
  • Ice
  • Heat
  • Hands-on adjustments
  • Non-force techniques
  • Electrical muscle stimulation
  • Massage
  • Special instrument applications
  • Traction

The Whole-Body Wellness Advantage

Whole body wellness is an integral part of chiropractic care. It can involve diet modification, lifestyle changes, exercise, and stress reduction practices.

When a chiropractor treats a cancer patient � or any patient � he or she will look beyond the obvious issues or symptoms to find the root of the problem and ways to help the body heal itself. Sometimes this may involve supplements, vitamins, or minerals that will aid in correcting the condition. Other times it may simply be a matter of getting the body to a healthy state where it is strong enough to combat the condition or heal from injury.

The treatment is individualized and tailored specifically to the patient�s needs and lifestyle. For instance, many conditions benefit from weight loss or exercise, and many pain issues respond well to adjustments in diet and stress reduction. Chiropractic looks at the whole body and works to provide it with what it needs to get strong and get healthy.

Chiropractor Recommended

CBD – Cannabidiol’s Life Changing Properties

CBD – Cannabidiol’s Life Changing Properties

CBD�research currently being conducted is showing its medical potential. This has opened doors for antipsychotic, anticancer and anti-inflammatory�treatment options among a variety of others. Scientists from all over are publishing studies that are proving CBD is one of the most effective and favorable cannabinoids that promotes proper function of the body’s systems.

Five Properties Of CBD

CBD Medical Benefits

cbd - cannabidiol el paso tx.

1. Inhibits Cancer Cell Growth

Studies have supported this claim. By way of Proapoptotic action or apoptosis, Cannabidiol, Tetrahydrocannabinol, Cannabigerol and Cannabichromene�in this order are extremely effective in tumor growth reduction in rats and cancerous human prostate cells. Research is still ongoing, but understanding that these cannabinoids stimulate the body�s process of killing cells that no longer function properly or at their optimal level. In traditional chemotherapy both�healthy and cancerous cells�are destroyed and only works when the cancer cells are replicating more frequently than healthy cells. CBD treatment promotes the body�s natural immune response to cells that are not functioning properly, which eradicates tumors.

2. Pain Reducer

The most common reason people start using marijuana despite its psychoactive affects, is that it also functions, as a pain reliever! People with chronic pain that are tired of taking pain killing opiates, rely on cannabinoid products to deal with pain and eliminate its source, commonly inflammation. Inflammation is the body�s natural response to injury, which floods the injured area with blood and nutrients to aid in rehabilitation. But inflammation creates secondary problems, among them�pain and discomfort. Through stimulation of nutrients in the area that is injured, CBD creates negative feedback to inflammatory reactions, as the nutrients that came with the inflammation are already there.

cbd - cannabidiol el paso tx.

3. Treats Anxiety

Anxiety along with PTSD affects over 40 million adults in the U.S. Valium and Xanax is what is normally used to treat these conditions. However, CBD products are becoming the preferred treatment, as they have none of the side effects or dependency issues. The effects of CBD have been observed thoroughly by experts and studies have proved its effectiveness, as a dependable alternative for mental disorders. Two receptors in the human brain responsible for sending out Adrenaline and Serotonin are the�?2-adrenergic receptor agonist and 5-HT1A receptor antagonist. These receptors both are related to anxiety, depression, insomnia, and other mental disorders when imbalanced.

4. Strengthens The Immune System

Phytocannabinoids are able to balance, reinforce and strengthen the immune system. Cannabinoid products taken daily, work in regulating the immune system. This increases the body�s detection of foreign and potentially dangerous organisms, which include cancer cells.

5. Prevents Muscle Spasms

CBD contains�chemically antispasmodic properties. Athletes from all sports love CBD and what it can do. It is a preferred supplement and these oils have proven to prevent muscle spasms and soreness. This is done through�lubricating the potassium and calcium pumps within the muscle tissue.

CBD is finding its place, slowly, but surely. It is one of natures own medicines and it is our job to discover and figure how to utilize these properties. Consult a doctor before beginning any treatment of diagnosed or undiagnosed diseases with CBD. For the more severe diseases like diabetes, schizophrenia, epilepsy, which, CBD can treat, but only when used properly.

Medical Benefits

cbd - cannabidiol el paso tx.

Prostate Cancer, Nutrition And Dietary Interventions

Prostate Cancer, Nutrition And Dietary Interventions

Prostate Cancer: Abstract

Prostate cancer (PCa) remains a leading cause of mortality in US men and the prevalence continues to rise world-wide especially in countries where men consume a �Western-style� diet. Epidemiologic, preclinical and clinical studies suggest a potential role for dietary intake on the incidence and progression of PCa. ‘This minireview provides an overview of recent published literature with regard to nutrients, dietary factors, dietary patterns and PCa incidence and progression. Low carbohydrates intake, soy protein, omega-3 (w-3) fat, green teas, tomatoes and tomato products and zyflamend showed promise in reducing PCa risk or progression. A higher saturated fat intake and a higher ?-carotene status may increase risk. A �U� shape relationship may exist between folate, vitamin C, vitamin D and calcium with PCa risk. Despite the inconsistent and inconclusive findings, the potential for a role of dietary intake for the prevention and treatment of PCa is promising. The combination of all the beneficial factors for PCa risk reduction in a healthy dietary pattern may be the best dietary advice. This pattern includes rich fruits and vegetables, reduced refined carbohydrates, total and saturated fats, and reduced cooked meats. Further carefully designed prospective trials are warranted.

Keywords: Diet, Prostate cancer, Nutrients, Dietary pattern, Lifestyle, Prevention, Treatment, Nutrition, Dietary intervention, Review

Introduction: Prostate Cancer

Prostate cancer (PCa) is the second most common cancer in men, with nearly a million new cases diagnosed worldwide per year [1], with approximately a six-fold higher incidence in Western than in non-Western countries. Diet, lifestyle, environmental and genetic factors are hypothesized to play a role in these differences. This review focuses on the latest evidence of the potential role of dietary factors on PCa and includes epidemiologic and clinical trial evidence for the impact of protein, fat, carbohydrate, fiber, phytochemicals, other food components, whole foods and dietary patterns on PCa incidence, development and/or progression. Data from meta-analyses or well-designed randomized trials and prospective studies are emphasized in this review. It should be noted that studies of dietary intake or nutrition and cancer are often subject to various limitations and thus complicate interpretation of results. For example, when a study is designed to examine the effect of the amount of fat intake, alteration in fat intake inevitably will change intake of protein and/or carbohydrate, and may change the intake of other nutrients as well. As a result, it is difficult to attribute the effect to change in fat intake alone. In addition, the impact of macronutrients potentially involves aspects of both absolute quantity and the type of macronutrients consumed. Both aspects may potentially affect cancer initiation and/or development independently, but they are not always distinguishable in research designs. Though this topic was recently reviewed [2], given the extensive new literature on the topic, an updated review is presented herein and a summary table is provided for a quick reference (Table 1).

Nutrients Carbohydrates Given the hypothesis that insulin is a growth factor for PCa, it has been hypothesized that reducing carbohydrates and thus lowering serum insulin may slow PCa growth [3]. Indeed, in animal models, either a no-carbohydrate ketogenic diet (NCKD) [4,5] or a low-carbohydrate diet (20% kcal as carbohydrate) has favorable effects on slowing prostate tumor growth [6,7]. In human studies, one�study found that high intake of refined carbohydrates was associated with increased risk of PCa [7]. In addition to the amount of carbohydrates, type of carbohydrates may impact on PCa but research has been inconclusive. The potential to reduce PCa risk and progression via impacting carbohydrate metabolism is actively being investigated with Metformin. Metformin reduced PCa cell proliferation and delayed progression in vitro and in vivo, respectively [8-10] and reduced incident risk and mortality in humans [11-13]. Two single arm clinical trials also showed a positive effect of metformin in affecting markers of PCa proliferation and progression [14,15]. However, other retrospective cohort studies have not supported an effect of metformin on recurrence or incident risk of PCa [16-22]. Despite the potential for reducing either total or simple carbohydrates in benefiting PCa control, evidence is lacking from randomized controlled trials (RCT). Two randomized trials are on-going examining the impact of a low-carbohydrate diet (approximately 5% kcal) on the PSA doubling time among PCa patients post radical prostatectomy (NCT01763944) and on glycemic response among patients initiating androgen deprivation therapy (ADT) (NCT00932672 ). Findings from these trials will shed light on the effect of carbohydrate intake on markers of PCa progression and the role of reduced carbohydrate intake on offsetting the side effects of ADT.

Protein

The ideal level of protein intake for optimal overall health or prostate health is unclear. Despite the popularity of low carbohydrate diets that are high in protein, recent human studies reported that low protein intake was associated with lower risk for cancer and overall mortality among men 65 and younger. Among men older than 65, low protein intake was associated with a higher risk for cancer and overall mortality [23]. In animal models the ratio between protein and carbohydrate impacted on cardiometabolic health, aging and longevity [24]. The role of dietary protein and the protein to carbohydrate ratio on PCa development and progression requires further study.

Animal-Based Proteins

Studying protein intake, like all aspects of nutritional science, can be challenging. For example, animal meat, which is a source of protein in Western diets, is composed not only of protein, but also of fat, cholesterol, minerals and other nutrients. The amount of these nutrients including fatty acids may vary from one animal meat to the other. Previous studies in human have shown that consumption of skinless poultry, which is lower in cholesterol and saturated fat than many red meats, was not associated with the recurrence or progression of PCa [25]. However, consumption of baked poultry was inversely associated with advanced PCa [26,27], while cooked red meat was associated with increased advanced PCa risk [26,27]. Thus, how the food is prepared may modify its impact on PCa risk and progression. Overall, fish consumption may be associated with reduced PCa mortality, but high temperature cooked fish may contribute to PCa carcinogenesis [28]. Thus, it may be advisable to consume fish regularly but cooking temperature should be kept moderate.

Dairy-Based Protein

Another common protein source is dairy products, such as milk, cheese and yogurt. Previous studies have shown that dairy increased overall PCa risk but not with aggressive or lethal PCa [29,30]. In addition, both whole milk and low-fat milk consumption were reported to either promote or delay PCa progression [29,31]. In the Physicians Health follow up cohort with 21,660 men, total dairy consumption was found to be associated with increased PCa incidence [32]. In particular, low fat or skim milk increased low grade PCa, whereas whole milk increased fatal PCa risk. Though the exact component(s) of dairy products driving these associations is unknown, the high concentrations of saturated fat and calcium may be involved. A cross-sectional study of 1798 men showed that dairy protein was positively associated with serum IGF-1 [33] levels which may stimulate initiation or progression of PCa. Thus, further research is needed to clarify the relationship between dairy intake and PCa. There is insufficient data to provide recommendations specifically related to dairy or dairy protein and PCa risk or progression.

Plant-Based Proteins

Soy and soy-based products are rich in protein and phytoestrogens that may facilitate PCa prevention, but its role on PCa is unclear. In a study in mice, intake of soy products was associated with decreased hepatic aromatase, 5?-reductase, expression of androgen receptor and its regulated genes, FOXA1, urogenital tract weight and PCa tumor progression [34]. A recent randomized trial of 177 men with high-risk disease after radical prostatectomy found that soy protein supplementation for two years had no effect on risk of PCa recurrence [35]. Although epidemiological and pre-clinical studies [36,37] support a potential role for soy/soy isoflavones in PCa risk reduction or progression, a meta-analysis did not find significant impact of soy intake in PSA levels, sex hormone-binding globulin, testosterone, free testosterone, estradiol or dihydrotestosterone [38]. Another RCT in patients before prostatectomy also did not find any effect of soy isoflavone supplement up to six weeks on PSA, serum total testosterone, free testosterone, total estrogen, estradiol or total cholesterol [39]. Since most RCTs�conducted have been small and of short duration, further examination is needed.

Many studies have continued to examine the primary isoflavone in soy, genistein, and its effect on PCa. The potential for genistein to inihibit PCa cell detachment, invasion and metastasis is reported [40]. Genistein may modify glucose update and glucose transporter (GLUT) expression in PCa cells [41], or exert its anti-tumor effect by down regulating several microRNAs [42]. Studies using tumor cells and animal models suggest genistein may compete with and block endogenous estrogens from binding to the estrogen receptor, thereby inhibiting cellular proliferation, growth, and inducing differentiation and, specifically, genistein may inhibit cell detachment, protease production, cell invasion and thus prevent metastasis [36,40,43]. However, neither plasma nor urinary genistein levels were associated with PCa risk in case control studies [44,45]. In a phase 2 placebo-controlled RCT with 47 men, supplementation of 30 mg genistein for three to six weeks significantly reduced androgen-related markers of PCa progression [46]. In addition, genistein may be beneficial in improving cabazitaxel chemotherapy in metastatic castration-resistant PCa [37]. Clinical studies are warranted to further examine the role of soy and soy isoflavones for PCa prevention or treatment. A definitive recommendation regarding protein intake for PCa prevention or treatment is not available yet.

Fat

Research findings examining fat consumption with PCa risk or progression are conflicting. Both the total absolute intake [47] of dietary fat and the relative fatty acid composition may independently relate to PCa initiation and/or progression. While animal studies repeatedly show that reducing dietary fat intake slows tumor growth [48-50] and high fat diets, especially animal fat and corn oil increase PCa progression [51], human data are less consistent. Case�control studies and cohort studies have shown either no association between total fat consumption and PCa risk [52-55] or an inverse association between fat intake and PCa survival, particularly among men with localized PCa [47]. In addition, a cross-sectional study showed that fat intake expressed as percent of total calorie intake was positively associated with PSA levels in 13,594 men without PCa [56]. Given these conflicting data, it is possible that the type of fatty acid [56] rather than total amount may play an important role in PCa development and progression. A study found plasma saturated fatty acids to be positively associated with PCa risk in a prospective cohort of 14,514 men of the Melbourne Collaborative Cohort Study [57]. In addition, another study found that eating more plant-based fat was associated with reduced PCa risk [58]. These studies support the current dietary guideline of eating less animal-based fat and more plant-based fat.

The data regarding omega-6 (w-6) and omega-3 (w-3) polyunsaturated fatty acid (PUFA) consumption and PCa risk are also conflicting. While there are data to support a link between increased w-6 PUFA intake (mainly derived from corn oil) and risk of overall and high-grade PCa [57,59], not all data support such a link [60]. In fact, a greater polyunsaturated fat intake was associated with a lower all cause mortality among men with nonmetastatic PCa in the Health Professionals Follow-up study [58]. The postulated mechanism linking w-6 PUFAs and PCa risk is the conversion of arachidonic acid (w-6 PUFA) to eicosanoids (prostaglandin E-2, hydroxyeicosatetraenoic acids and epoxyeicosatrienoic acids) leading to inflammation and cellular growth [61]. Conversely, w-3 PUFAs, which are found primarily in cold water oily fish, may slow growth of PCa through a number of mechanisms [61-63]. In a study of 48 men with low risk PCa under active surveillance, repeat biopsy in six months showed that prostate tissue w-3 fatty acids, especially eicosapentaenoic acid (EPA), may protect against PCa progression [64]. In vitro and animal studies suggest that w-3 PUFAs induce anti-inflammatory, pro-apoptotic, antiproliferative and anti-angiogenic pathways [65,66]. Moreover, a mouse study comparing various types of fat found that only the fish oil diet (that is, omega-3 based diet) slowed PCa growth relative to other dietary fats [67]. In regards to human data, a phase II randomized trial showed that a low-fat diet with w-3 supplementation four to six weeks prior to radical prostatectomy decreased PCa proliferation and cell cycle progression (CCP) score [62,68]. A low-fat fish oil diet resulted in decreased 15(S)- hydroxyeicosatetraenoic acid levels and lowered CCP score relative to a Western diet [69]. The potential benefits of omega-3 fatty acids from fish are supported by epidemiological literature showing that w-3 fatty acid intake was inversely associated with fatal PCa risk [70,71]. Despite the promise of omega-3 fatty acids, not all studies agree. Supplementing 2 g alpha-linolenic acid (ALA) per day for 40 months in 1,622 men with PSA <4 ng/ml did not change their PSA [72]. However, another study found that a high blood serum n-3 PUFA and docosapentaenoic acid (DPA) was associated with reduced total PCa risk while high serum EPA and docosahexaenoic acid (DHA) was possibly associated with increased high-grade PCa risk [73]. Further research is required to understand better the role of omega-3 PUFAs in PCa prevention or treatment.

Cholesterol

Many pre-clinical studies have shown that the accumulation of cholesterol contributes to the progression of PCa [74-76]. It was suggested that a high cholesterol in Lin et al. BMC Medicine (2015) 13:3 Page 5 of 15 circulation may be a risk factor for solid tumors, primarily through the upregulation of cholesterol synthesis, inflammatory pathways [77] and intratumoral steroidogenesis [78]. According to a recent study with 2,408 men scheduled for biopsy, serum cholesterol was independently associated with prediction of PCa risk [79]. Consistent with the cholesterol findings, usage of the cholesterol lowering drug statin post radical prostatectomy (RP) was significantly associated with reduced risk of biochemical recurrence in 1,146 radical prostatectomy patients [80]. Another study also showed that statins may reduce PCa risk by lowering progression [81]. Although the mechanism has not been established, more recent studies also showed that a low high-density lipoprotein (HDL) cholesterol level was associated with a higher risk for PCa and, thus, a higher HDL was protective [81-84]. These findings support the notion that a heart-healthy dietary intervention that lowers cholesterol may benefit prostate health also.

Vitamins & Minerals

Herein we will review the recent data on vitamins A, B complex, C, D, E, and K and selenium. In the two large clinical trials: the Carotene and Retinol Efficacy Trial (CARET; PCa was a secondary outcome) and the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health prospective cohort study, excessive multivitamin supplementation was associated with a higher risk of developing aggressive PCa, particularly among those taking individual ?-carotene supplements [85,86]. Similarly, high serum ?-carotene levels were associated with a higher risk for PCa among 997 Finnish men in the Kuopio Ischaemic Heart Disease Risk Factor cohort [87]. However, ?-carotene supplement was not found to affect risk for lethal PCa during therapy [88], or in the Danish prospective cohort study of 26,856 men [89]. Circulating retinol also was not associated with PCa risk in a large case�control study [90]. Thus, the association between vitamin A and PCa is still unclear.

Preclinical evidence suggests folate depletion may slow tumor growth, while supplementation has no effect on growth or progression, but may directly lead to epigenetic changes via increases in DNA methylation [91]. Two meta-analyses also showed that circulating folate levels were positively associated with an increased risk of PCa [92,93], while dietary or supplemental folate had no effect on PCa risk [94] in a cohort study with 58,279 men in the Netherlands [95] and a case�control study in Italy and Switzerland [96]. In fact, one study of a cohort of men undergoing radical prostatectomy at several Veterans Administration facilities across the US even showed that higher serum folate levels were associated with lower PSA and, thus, lower risk for biochemical failure [97]. Another study using data from the 2007 to 2010 National Health and Nutrition Examination Survey showed that a higher folate status may be protective against elevated PSA levels among 3,293 men, 40-years old and older, without diagnosed PCa [98]. It was suggested that folate may play a dual role in prostate carcinogenesis and, thus, the complex relationship between folate and PCa awaits further investigation [99].

Despite the potential role of vitamin C (ascorbic acid) as an antioxidant in anticancer therapy, trials examining dietary intake or supplementation of vitamin C are few. A RCT showed no effect of vitamin C intake on PCa risk [89]. Furthermore, vitamin C at high doses may act more as a pro-oxidant than antioxidant, complicating the research design and interpretation.

The primary active form of vitamin D, 1,25 dihydroxyvitamin D3 (calcitriol) aids in proper bone formation, induces differentiation of some immune cells, and inhibits pro-tumor pathways, such as proliferation and angiogenesis, and has been suggested to benefit PCa risk [100]; however, findings continue to be inconclusive. More recent studies found that increased serum vitamin D levels were associated with decreased PCa risk [101,102]. Further, supplementing vitamin D may slow PCa progression or induce apoptosis in PCa cells [103-105]. Other studies, however, reported either no impact of vitamin D supplement on PSA [106] or no effect of vitamin D status on PCa risk [107,108]. Some studies contrarily reported that a lower vitamin D status was associated with a lower PCa risk in older men [109], or a higher serum vitamin D was associated with a higher PCa risk [110,111]. A study even suggested that a �U� shaped relationship may exist between vitamin D status and PCa and the optimal range of circulating vitamin D for PCa prevention may be narrow [112]. This is consistent with the findings for other nutrients that a greater intake of a favorable nutrient may not always be better.

A recent study showed that the association between vitamin D and PCa was modulated by vitamin D-binding protein [113] which may have partially explained the previous inconsistent findings. Further, a meta-analysis investigating the association between Vitamin D receptor (VDR) polymorphisms (BsmI and FokI) and PCa risk reported no relationship with PCa risk [114]. Thus, the role of vitamin D in PCa remains unclear.

In a large randomized trial with a total of 14,641 US male physicians ?50-years old, participants randomly received 400 IU of vitamin E every other day for an overall mean of 10.3 (13.8) years. Vitamin E supplementation had no immediate or long-term effects on the risk of total cancers or PCa [115]. However, a moderate dose of vitamin E supplement (50 mg or about 75 IU) resulted in lower PCa risk among 29,133 Finnish male smokers [116]. Multiple preclinical studies suggest vitamin E slows tumor growth, partly due to inhibiting DNA synthesis and inducing�apoptotic pathways [117]. Unfortunately, human studies have been less than supportive. Two observational studies (the Cancer Prevention Study II Nutrition Cohort and the NIH-AARP Diet and Health Study) both showed no association between vitamin E supplementation and PCa risk [118,119]. However, a higher serum ?-tocopherol but not the ?-tocopherol level was associated with decreased risk of PCa [120,121] and the association may be modified by genetic variations in vitamin E related genes [122]. On the contrary, a prospective randomized trial, the Selenium and Vitamin E Cancer Prevention Trial (SELECT), showed vitamin E supplementation significantly increased PCa risk [123] and that a higher plasma ?-tocopherol level may interact with selenium supplements to increase high grade PCa risk [124]. This finding is consistent with a case-cohort study of 1,739 cases and 3,117 controls that showed vitamin E increased PCa risk among those with low selenium status but not those with high selenium status [125]. Thus, more research is needed to examine the association between vitamin E and PCa and the dose effect and interaction with other nutrients should be considered.

Vitamin K has been hypothesized to help prevent PCa by reducing bioavailable calcium. Preclinical studies show the combination of vitamins C and K have potent antitumor activity in vitro and act as chemo- and radiosensitizers in vivo [126]. To date, few studies have investigated this, although one study using the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort found an inverse relationship between vitamin K (as menaquinones) intake and PCa incidence [127]. Little to no preclinical studies have been conducted to examine the role of calcium with PCa. Retrospective and meta-analyses suggest increased or reduced PCa risk with increased calcium intake, while others suggest no association [128,129]. Another study suggests a �U�-shaped association, where very low calcium levels or supplementation are both associated with PCa [130].

Selenium, on the other hand, has been hypothesized to prevent PCa. While in vitro studies suggested that selenium inhibited angiogenesis and proliferation while inducing apoptosis [131], results from SELECT showed no benefit of selenium alone or in combination with vitamin E for PCa chemoprevention [123]. Further, selenium supplementation did not benefit men with low selenium status but increased the risk of high-grade PCa among men with high selenium status in a randomly selected cohort of 1,739 cases with high-grade (Gleason 7�10) PCa and 3,117 controls [125]. A prospective Netherlands Cohort Study, which included 58,279 men, 55- to 69-years old, also showed that toenail selenium was associated with a reduced risk of advanced PCa [132]. Further research is needed to clarify the role of selenium with PCa.

Phytochemicals

Along with vitamins and minerals [2], plants contain phytochemicals with potential anti-cancer effects. Typically not considered essential compounds, phytochemicals have antioxidant and anti-inflammatory properties.

Silibinin is a polyphenolic flavonoid found in the seeds of milk thistle. It has been shown in vitro and in vivo to inhihit PCa growth by targeting epidermal growth factor receptor (EGFR), IGF-1 receptor (IGF-1R), and nuclear factor-kappa B (NF-kB) pathways [133,134]. A recent study showed that silibinin may be useful in PCa prevention by inhibiting TGF?2 expression and cancerassociated fibroblast (CAF)-like biomarkers in the human prostate stromal cells [135]. Thus, silibinin is a promising candidate as a PCa chemopreventive agent that awaits further research.

Curcumin is used as food additive in Asia and as an herbal medicine for inflammation [136]. In vitro, curcumin inhibits the pro-inflammatory protein NF-?B while inducing apoptosis through increased expression of proapoptotic genes [137]. In vivo, curcumin slows PCa growth in mice while sensitizing tumors to chemo- and radiotherapies [136]; however, no human trial has examined its impact on PCa.

Pomegranate

The peel and fruit of pomegranates and walnuts are rich in ellagitannins (punicalagins). These phytochemicals are readily metabolized to the active form ellagic acid by gut flora [138]. Preclinical experiments show ellagitannins inhibit PCa proliferation and angiogenesis under hypoxic conditions and induce apoptosis [137,138]. In prospective trials in men with a rising PSA after primary treatment, pomegranate juice or POMx, a commercially available pomegranate extract, increased the PSA doubling time relative to baseline [139,140], although no trials included a placebo group. Results are pending from a prospective placebo RCT using pomegranate extract in men with a rising PSA. However, in a placebo controlled trial, two pills of POMx daily for up to four weeks prior to radical prostatectomy had no impact on tumor pathology or oxidative stress or any other tumor measures [141].

Green Tea

Green tea contains a number of antioxidant polyphenols including catechins, such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), (?)-epicatechin-3-gallate (ECG) and (?)-epicatechin. Preclinical studies suggest EGCG inhibits PCa growth, induces intrinsic and extrinsic apoptotic pathways and decreases inflammation by inhibiting NFkB [137]. Furthermore, the antioxidant properties of EGCG are 25 to 100 times more potent than vitamins C and E [131]. In a prospective randomized preprostatectomy trial, men consuming brewed green tea Lin et al. BMC Medicine (2015) 13:3 Page 7 of 15 prior to surgery had increased levels of green tea polyphenols in their prostate tissue [142]. In a small proof-ofprinciple trial with 60 men, daily supplementation of 600 mg green tea catechin extract reduced PCa incidence by 90% (3% versus 30% in the placebo group) [143]. Another small trial also showed that EGCG supplement resulted in a significant reduction in PSA, hepatocyte growth factor and vascular endothelial growth factor in men with PCa [144]. These studies suggest green tea polyphenols may lower PCa incidence and reduce PCa progression but more research is needed to confirm and clarify its mechanism [137,143,145].

Resveratrol

While most in vitro studies suggest resveratrol inhibits PCa growth [146-148], resveratrol suppresses tumor growth in some [137] but not all animal models [149], possibly due to limited bioavailability [150,151]. To date, there are no clinical trials investigating the preventive or therapeutic effects of resveratrol on PCa.

Zyflamend

Zyflamend is an anti-inflammatory mixture of herbs that has been shown to reduce PCa progression by lowering the expression of markers including pAKT, PSA, histone deacetylases and androgen receptor in animal models and PCa cell line [152-154]. Despite its anti-cancer potential [155], very few studies have been conducted in humans [156,157]. In an open-label Phase I trial of 23 patients with high-grade prostatic intraepithelial neoplasia, Zyflamend alone or in conjunction with other dietary supplements for 18 months reduced the risk for developing PCa [156]. More RCTs in humans are needed to confirm the efficacy and clinical application of this herbal supplement.

Other Whole Foods Fruits & Vegetables

Fruits and vegetables are rich sources of vitamins, minerals and phytochemicals. Several epidemiologic studies found inverse relationships between total fruit and vegetable intake [158], and cruciferous vegetable intake and PCa risk [159,160]. Allium vegetables, such as garlic, leeks, chives, and shallots, contain multiple sulfurous phytochemicals that were suggested to enhance the immune system, inhibit cell growth, modulate expression of androgen-responsive genes and induce apoptosis [161]. Although the number of published studies is limited, both preclinical and epidemiologic data suggest allium vegetable intake may be protective against PCa, particularly localized disease [162]. A randomized trial with 199 men also found that a blend supplement of pomegranate, green tea, broccoli and turmeric significantly reduced the rate of rise in PSA in men with PCa [163].

Tomatoes & Tomato Products

A number of studies have examined the association between tomatoes and tomato products with PCa but the findings are inconclusive. The antioxidant lycopene, which is rich in tomatoes, has also been studied specifically for its impact on PCa. In vitro, lycopene halts the cell cycle in several PCa cell lines and decreases IGF-1 signaling by inducing IGF-1 binding proteins [131]. While some animal studies found lycopene specifically slows PCa growth [164] or reduces PCa epithelial cells at stages of initiation, promotion and progression [165], two studies found conflicting findings between tomato paste and lycopene [166,167]. Prospective human studies found higher lycopene consumption [168,169] or higher serum levels were associated with lower PCa risk [170], but others have not [171,172]. Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PCa at six-month follow-up biopsy (P = 0.003) [173]. Two short-term preprostatectomy trials using tomato sauce or lycopene supplementation demonstrated lycopene uptake in prostate tissue and antioxidant and potential anticancer effects [174,175]. While several clinical trials suggested an inverse relationship between lycopene supplementation, PSA levels and decreases in cancerrelated symptoms [171,176], no large-scale randomized trials have tested the role of lycopene or tomato products on PCa prevention or treatment.

Coffee

Coffee contains caffeine and several unidentified phenolic compounds that may serve as antioxidants. Epidemiological studies suggest an inverse relationship between coffee consumption and PCa risk, mainly for advanced or lethal stage disease, and the findings were independent of caffeine content [177,178]. Although several epidemiological studies [179-182] found no association between coffee consumption and PCa risk, a recent meta-analysis of prospective studies concluded that coffee consumption may reduce PCa risk [183]. The potential mechanism(s) and pathway(s) involved are unknown but may include antioxidant, anti-inflammatory effects, glucose and insulin metabolism, and potential impact on IGF-I and circulating sex hormones.

Dietary Patterns

Even though many single nutrients or food factors have been examined for their impact or association with PCa risk or progression, the results have largely been inconclusive. A potential reason for the inconsistency is the fact that the impact of single nutrient or food factor may be too small to be detected. In addition, nutrients naturally existing in foods often are highly correlated and may interact with each other and, thus, affect the impact on PCa. Thus, dietary pattern analysis has received an increasing Lin et al. BMC Medicine (2015) 13:3 Page 8 of 15 interest but research has been limited and the existing results have been inconclusive. In a cohort of 293,464 men, a high dietary quality, as indicated by the Healthy Eating Index (HEI) score, was associated with a lower risk of total PCa risk [70]. The Mediterranean diet, which is high in vegetables, olive oil, complex carbohydrates, lean meats and antioxidants, is consistently recommended to patients for prevention of cardiovascular disease and obesity [184], and may show promise in PCa prevention [185]. Fish and omega-3 fatty acid consumption in the Mediterranean pattern were significantly and inversely associated with fatal PCa risk. In addition, adherence to the Mediterranean diet after diagnosis of non-metastatic PCa was associated with lower overall mortality [186]. Whereas, a Western pattern with high intakes of red meats, processed meats, fried fish, chips, high-fat milk and white bread, was associated with a higher risk for PCa [187].

Furthermore, Asian countries with high consumption of omega-3 PUFAs, soy and green tea-based phytochemicals, have lower PCa incidences versus countries consuming a �Western-style� diet [188]. However, not all studies [189-191] supported an association between certain dietary pattern and risk of PCa. It is possible that the methodology used in identifying dietary patterns may not have captured all the dietary factors associated with PCa risk. Alternatively, each dietary pattern may contain both beneficial and harmful components resulting in an overall null association. More research is needed to continue searching for dietary patterns that combine most of the beneficial nutrients/food factors for PCa and limit most of the negative nutrients/ food factors.

Future Direction For Clinical Trials

Based on the multitude of epidemiologic, preclinical and clinical trials described in this review, dietary interventions for the prevention and treatment of PCa hold great promise. In addition, several dietary factors and vitamins/supplements may be associated with PCa risk and/ or progression of disease. Prospective randomized trials are clearly indicated to identify specific nutrients or combination therapies for the prevention and treatment of PCa.

Recently, active surveillance (AS) has emerged as a viable option for men with lower risk PCa. Men on AS are motivated to adhere to diet and lifestyle modifications [192], making this subset a good target for dietary intervention and quality of life trials [193]. PCa survivors who are more active and report �healthy� eating habits (that is, consuming low-fat, low-refined carbohydrate diets rich in fruits and vegetables) have better overall quality of life versus their inactive, unhealthy counterparts [194]. Thus, more randomized trials are warranted to determine the overall long-term effects of dietary intervention in this population. Specifically, key questions to address in future trials are: 1) Can dietary interventions delay the need for treatment in men on AS; 2) Can dietary interventions prevent recurrence for men after treatment; 3) Can dietary interventions delay progression among men with recurrent disease and, thus, delay the need for hormonal therapy; 4) Can dietary interventions reduce the side effects of PCa treatments including hormonal therapy and newer targeted therapies; and 5) Is there any role for dietary interventions alone or combined with targeted therapies in men on hormonal therapy to prevent castrate-resistance or after the emergence of castrate resistance disease? Because increasing evidence shows that metabolic abnormalities increase risk for PCa, lifestyle intervention that improves metabolic profile is a win-win option for PCa prevention and treatment [195,196].

Conclusions: Prostate Cancer

Future research is required to determine the ideal diet for PCa prevention or treatment. However, several dietary factors and some dietary patterns hold promise in reducing PCa risk or progression and are consistent with current dietary guidelines for Americans [197]. For counseling patients on diet for primary and secondary PCa prevention, many believe �heart healthy equals prostate healthy.� Thus, given the current inconclusive results, the best dietary advice for PCa prevention or management seems to include: increasing fruits and vegetables, replacing refined carbohydrates with whole grains, reducing total and saturated fat, reducing overcooked meats and consuming a moderate amount of calories or reducing carbohydrates with a primary goal of obtaining and maintaining a healthy body weight.

Competing interests The authors declare that they have no competing interests.

Authors� contributions P-HL and SF conducted the review, P-HL drafted the manuscript and SF and WA edited and provided critical input. All authors read and approved the final manuscript.

Acknowledgements Funding was provided by grants 1K24CA160653 (Freedland), NIH P50CA92131 (W. Aronson). This manuscript is the result of work supported with resources and the use of facilities at the Veterans Administration Medical Center, West Los Angeles (W. Aronson).

Author details 1 Department of Medicine, Division of Nephrology, Duke University Medical Center, Box 3487, Durham, NC 27710, USA. 2 Urology Section, Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA. 3 Department of Urology, UCLA School of Medicine, Los Angeles, CA, USA. 4 Urology Section, Department of Surgery, Durham Veterans Affairs Medical Center, Division of Urology, Durham, NC, USA. 5 Duke Prostate Center, Departments of Surgery and Pathology, Duke University Medical Center, Durham, NC, USA.

 

blank
References:

1. Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, Bray F:
International variation in prostate cancer incidence and mortality rates.
Eur Urol 2012, 61:1079�1092.
2. Masko EM, Allott EH, Freedland SJ: The relationship between nutrition and
prostate cancer: is more always better? Eur Urol 2013, 63:810�820.
3. Mavropoulos JC, Isaacs WB, Pizzo SV, Freedland SJ: Is there a role for a
low-carbohydrate ketogenic diet in the management of prostate cancer?
Urology 2006, 68:15�18.
4. Freedland SJ, Mavropoulos J, Wang A, Darshan M, Demark-Wahnefried W,
Aronson WJ, Cohen P, Hwang D, Peterson B, Fields T, Pizzo SV, Isaacs WB:
Carbohydrate restriction, prostate cancer growth, and the insulin-like
growth factor axis. Prostate 2008, 68:11�19.
5. Mavropoulos JC: Buschemeyer WC 3rd, Tewari AK, Rokhfeld D, Pollak M,
Zhao Y, Febbo PG, Cohen P, Hwang D, Devi G, Demark-Wahnefried W,
Westman EC, Peterson BL, Pizzo SV, Freedland SJ: The effects of varying
dietary carbohydrate and fat content on survival in a murine LNCaP
prostate cancer xenograft model. Cancer Prev Res (Phila Pa) 2009,
2:557�565.
6. Masko EM, Thomas JA 2nd, Antonelli JA, Lloyd JC, Phillips TE, Poulton SH,
Dewhirst MW, Pizzo SV, Freedland SJ: Low-carbohydrate diets and
prostate cancer: how low is �low enough�? Cancer Prev Res (Phila) 2010,
3:1124�1131.
7. Drake I, Sonestedt E, Gullberg B, Ahlgren G, Bjartell A, Wallstrom P, Wirf�lt E:
Dietary intakes of carbohydrates in relation to prostate cancer risk: a
prospective study in the Malmo Diet and Cancer cohort. Am J Clin Nutr
2012, 96:1409�1418.
8. Zhang J, Shen C, Wang L, Ma Q, Xia P, Qi M, Yang M, Han B: Metformin
inhibits epithelial-mesenchymal transition in prostate cancer cells:
Involvement of the tumor suppressor miR30a and its target gene SOX4.
Biochem Biophys Res Commun 2014, 452:746�752.
9. Lee SY, Song CH, Xie YB, Jung C, Choi HS, Lee K: SMILE upregulated by
metformin inhibits the function of androgen receptor in prostate cancer
cells. Cancer Lett 2014, 354:390�397.
10. Demir U, Koehler A, Schneider R, Schweiger S, Klocker H: Metformin antitumor
effect via disruption of the MID1 translational regulator complex
and AR downregulation in prostate cancer cells. BMC Cancer 2014, 14:52.
11. Margel D: Metformin to prevent prostate cancer: a call to unite. Eur Urol
2014. doi:10.1016/j.eururo.2014.05.012. [Epub ahead of time]
12. Margel D, Urbach DR, Lipscombe LL, Bell CM, Kulkarni G, Austin PC, Fleshner
N: Metformin use and all-cause and prostate cancer-specific mortality
among men with diabetes. J Clin Oncol 2013, 31:3069�3075.
13. Tseng CH: Metformin significantly reduces incident prostate cancer risk
in Taiwanese men with type 2 diabetes mellitus. Eur J Cancer 2014,
50:2831�2837.
14. Joshua AM, Zannella VE, Downes MR, Bowes B, Hersey K, Koritzinsky M,
Schwab M, Hofmann U, Evans A, van der Kwast T, Trachtenberg J, Finelli A,
Fleshner N, Sweet J, Pollak M: A pilot �window of opportunity�
neoadjuvant study of metformin in localised prostate cancer. Prostate
Cancer Prostatic Dis 2014, 17:252�258.
15. Rothermundt C, Hayoz S, Templeton AJ, Winterhalder R, Strebel RT, Bartschi
D, Pollak M, Lui L, Endt K, Schiess R, R�schoff JH, Cathomas R, Gillessen S:
Metformin in Chemotherapy-naive Castration-resistant Prostate Cancer:
A Multicenter Phase 2 Trial (SAKK 08/09). Eur Urol 2014, 66:468�474.
16. Allott EH, Abern MR, Gerber L, Keto CJ, Aronson WJ, Terris MK, Kane CJ,
Amling CL, Cooperberg MR, Moorman PG, Freedland SJ: Metformin does
not affect risk of biochemical recurrence following radical
prostatectomy: results from the SEARCH database. Prostate Cancer
Prostatic Dis 2013, 16:391�397.
17. Rieken M, Kluth LA, Xylinas E, Fajkovic H, Becker A, Karakiewicz PI, Herman
M, Lotan Y, Seitz C, Schramek P, Remzi M, Loidl W, Pummer K, Lee RK,
Faison T, Scherr DS, Kautzky-Willer A, Bachmann A, Tewari A, Shariat SF:
Association of diabetes mellitus and metformin use with biochemical
recurrence in patients treated with radical prostatectomy for prostate
cancer. World J Urol 2014, 32:999�1005.
18. Margel D, Urbach D, Lipscombe LL, Bell CM, Kulkarni G, Austin PC, Fleshner
N: Association between metformin use and risk of prostate cancer and
its grade. J Natl Cancer Inst 2013, 105:1123�1131.
19. Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini F, Nicolucci A:
Metformin therapy and risk of cancer in patients with type 2 diabetes:
systematic review. PLoS One 2013, 8:e71583.
20. Kaushik D, Karnes RJ, Eisenberg MS, Rangel LJ, Carlson RE, Bergstralh EJ:
Effect of metformin on prostate cancer outcomes after radical
prostatectomy. Urol Oncol 2014, 32:43 e41�47.
21. Bensimon L, Yin H, Suissa S, Pollak MN, Azoulay L: The use of metformin in
patients with prostate cancer and the risk of death. Cancer Epidemiol
Biomarkers Prev 2014, 23:2111�2118.
22. Tsilidis KK, Capothanassi D, Allen NE, Rizos EC, Lopez DS, van Veldhoven K,
Sacerdote C, Ashby D, Vineis P, Tzoulaki I, Ioannidis JP: Metformin does not
affect cancer risk: a cohort study in the U.K. Clinical Practice Research
Datalink analyzed like an intention-to-treat trial. Diabetes Care 2014,
37:2522�2532.
23. Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F,
Fontana L, Mirisola MG, Guevara-Aguirre J, Wan J, Passarino G, Kennedy BK,
Wei M, Cohen P, Crimmins EM, Longo VD: Low protein intake is associated
with a major reduction in IGF-1, cancer, and overall mortality in the 65
and younger but not older population. Cell Metab 2014, 19:407�417.
24. Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE, Cogger VC,
Warren A, Huang X, Pichaud N, Melvin RG, Gokarn R, Khalil M, Turner N,
Cooney GJ, Sinclair DA, Raubenheimer D, Le Couteur DG, Simpson SJ: The
ratio of macronutrients, not caloric intake, dictates cardiometabolic
health, aging, and longevity in ad libitum-fed mice. Cell Metab 2014,
19:418�430.
25. Richman EL, Stampfer MJ, Paciorek A, Broering JM, Carroll PR, Chan JM:
Intakes of meat, fish, poultry, and eggs and risk of prostate cancer
progression. Am J Clin Nutr 2010, 91:712�721.
26. Joshi AD, John EM, Koo J, Ingles SA, Stern MC: Fish intake, cooking
practices, and risk of prostate cancer: results from a multi-ethnic
case�control study. Cancer Causes Control 2012, 23:405�420.
27. Joshi AD, Corral R, Catsburg C, Lewinger JP, Koo J, John EM, Ingles SA,
Stern MC: Red meat and poultry, cooking practices, genetic susceptibility
and risk of prostate cancer: results from a multiethnic case�control
study. Carcinogenesis 2012, 33:2108�2118.
28. Catsburg C, Joshi AD, Corral R, Lewinger JP, Koo J, John EM, Ingles SA,
Stern MC: Polymorphisms in carcinogen metabolism enzymes, fish
intake, and risk of prostate cancer. Carcinogenesis 2012, 33:1352�1359.
29. Pettersson A, Kasperzyk JL, Kenfield SA, Richman EL, Chan JM, Willett WC,
Stampfer MJ, Mucci LA, Giovannucci EL: Milk and dairy consumption
among men with prostate cancer and risk of metastases and prostate
cancer death. Cancer Epidemiol Biomarkers Prev 2012, 21:428�436.
30. Deneo-Pellegrini H, Ronco AL, De Stefani E, Boffetta P, Correa P,
Mendilaharsu M, Acosta G: Food groups and risk of prostate cancer: a
case�control study in Uruguay. Cancer Causes Control 2012, 23:1031�1038.
31. Park SY, Murphy SP, Wilkens LR, Stram DO, Henderson BE, Kolonel LN:
Calcium, vitamin D, and dairy product intake and prostate cancer risk:
the Multiethnic Cohort Study. Am J Epidemiol 2007, 166:1259�1269.
32. Song Y, Chavarro JE, Cao Y, Qiu W, Mucci L, Sesso HD, Stampfer MJ,
Giovannucci E, Pollak M, Liu S, Ma J: Whole milk intake is associated with
prostate cancer-specific mortality among U.S. male physicians. J Nutr Feb
2013, 143:189�196.
33. Young NJ, Metcalfe C, Gunnell D, Rowlands MA, Lane JA, Gilbert R, Avery
KN, Davis M, Neal DE, Hamdy FC, Donovan J, Martin RM, Holly JM: A crosssectional
analysis of the association between diet and insulin-like growth
factor (IGF)-I, IGF-II, IGF-binding protein (IGFBP)-2, and IGFBP-3 in men in
the United Kingdom. Cancer Causes Control 2012, 23:907�917.
34. Christensen MJ, Quiner TE, Nakken HL, Lephart ED, Eggett DL, Urie PM:
Combination effects of dietary soy and methylselenocysteine in a mouse
model of prostate cancer. Prostate 2013, 73:986�995.
35. Bosland MC, Kato I, Zeleniuch-Jacquotte A, Schmoll J, Enk Rueter E,
Melamed J, Kong MX, Macias V, Kajdacsy-Balla A, Lumey LH, Xie H, Gao W,
Walden P, Lepor H, Taneja SS, Randolph C, Schlicht MJ, Meserve-Watanabe
H, Deaton RJ, Davies JA: Effect of soy protein isolate supplementation on
biochemical recurrence of prostate cancer after radical prostatectomy: a
randomized trial. JAMA 2013, 310:170�178.
36. Chiyomaru T, Yamamura S, Fukuhara S, Yoshino H, Kinoshita T, Majid S, Saini
S, Chang I, Tanaka Y, Enokida H, Seki N, Nakagawa M, Dahiya R: Genistein
inhibits prostate cancer cell growth by targeting miR-34a and oncogenic
HOTAIR. PLoS One 2013, 8:e70372.
37. Zhang S, Wang Y, Chen Z, Kim S, Iqbal S, Chi A, Ritenour C, Wang YA, Kucuk
O, Wu D: Genistein enhances the efficacy of cabazitaxel chemotherapy
in metastatic castration-resistant prostate cancer cells. Prostate 2013,
73:1681�1689.38. van Die MD, Bone KM, Williams SG, Pirotta MV: Soy and soy isoflavones in
prostate cancer: a systematic review and meta-analysis of randomized
controlled trials. BJU Int 2014, 113:E119�E130.
39. Hamilton-Reeves JM, Banerjee S, Banerjee SK, Holzbeierlein JM, Thrasher JB,
Kambhampati S, Keighley J, Van Veldhuizen P: Short-term soy isoflavone
intervention in patients with localized prostate cancer: a randomized,
double-blind, placebo-controlled trial. PLoS One 2013, 8:e68331.
40. Pavese JM, Krishna SN, Bergan RC: Genistein inhibits human prostate
cancer cell detachment, invasion, and metastasis. Am J Clin Nutr 2014,
100:431S�436S.
41. Gonzalez-Menendez P, Hevia D, Rodriguez-Garcia A, Mayo JC, Sainz RM:
Regulation of GLUT transporters by flavonoids in androgen-sensitive and
-insensitive prostate cancer cells. Endocrinology 2014, 155:3238�3250.
42. Hirata H, Hinoda Y, Shahryari V, Deng G, Tanaka Y, Tabatabai ZL, Dahiya R:
Genistein downregulates onco-miR-1260b and upregulates sFRP1 and
Smad4 via demethylation and histone modification in prostate cancer
cells. Br J Cancer 2014, 110:1645�1654.
43. Handayani R, Rice L, Cui Y, Medrano TA, Samedi VG, Baker HV, Szabo NJ,
Shiverick KT: Soy isoflavones alter expression of genes associated with
cancer progression, including interleukin-8, in androgen-independent
PC-3 human prostate cancer cells. J Nutr 2006, 136:75�82.
44. Travis RC, Allen NE, Appleby PN, Price A, Kaaks R, Chang-Claude J, Boeing H,
Aleksandrova K, Tj�nneland A, Johnsen NF, Overvad K, Ram�n Quir�s J,
Gonz�lez CA, Molina-Montes E, S�nchez MJ, Larra�aga N, Casta�o JM,
Ardanaz E, Khaw KT, Wareham N, Trichopoulou A, Karapetyan T, Rafnsson
SB, Palli D, Krogh V, Tumino R, Vineis P, Bueno-de-Mesquita HB, Stattin P,
Johansson M, et al: Prediagnostic concentrations of plasma genistein and
prostate cancer risk in 1,605 men with prostate cancer and 1,697
matched control participants in EPIC. Cancer Causes Control 2012,
23:1163�1171.
45. Jackson MD, McFarlane-Anderson ND, Simon GA, Bennett FI, Walker SP:
Urinary phytoestrogens and risk of prostate cancer in Jamaican men.
Cancer Causes Control 2010, 21:2249�2257.
46. Lazarevic B, Hammarstr�m C, Yang J, Ramberg H, Diep LM, Karlsen SJ,
Kucuk O, Saatcioglu F, Task�n KA, Svindland A: The effects of short-term
genistein intervention on prostate biomarker expression in patients with
localised prostate cancer before radical prostatectomy. Br J Nutr 2012,
108:2138�2147.
47. Epstein MM, Kasperzyk JL, Mucci LA, Giovannucci E, Price A, Wolk A,
H�kansson N, Fall K, Andersson SO, Andr�n O: Dietary fatty acid intake and
prostate cancer survival in Orebro County, Sweden. Am J Epidemiol 2012,
176:240�252.
48. Kobayashi N, Barnard RJ, Said J, Hong-Gonzalez J, Corman DM, Ku M,
Doan NB, Gui D, Elashoff D, Cohen P, Aronson WJ: Effect of low-fat diet on
development of prostate cancer and Akt phosphorylation in the Hi-Myc
transgenic mouse model. Cancer Res 2008, 68:3066�3073.
49. Ngo TH, Barnard RJ, Cohen P, Freedland S, Tran C, deGregorio F, Elshimali
YI, Heber D, Aronson WJ: Effect of isocaloric low-fat diet on human
LAPC-4 prostate cancer xenografts in severe combined immunodeficient
mice and the insulin-like growth factor axis. Clin Cancer Res 2003,
9:2734�2743.
50. Huang M, Narita S, Numakura K, Tsuruta H, Saito M, Inoue T, Horikawa Y,
Tsuchiya N, Habuchi T: A high-fat diet enhances proliferation of
prostate cancer cells and activates MCP-1/CCR2 signaling. Prostate 2012,
72:1779�1788.
51. Chang SN, Han J, Abdelkader TS, Kim TH, Lee JM, Song J, Kim KS, Park JH,
Park JH: High animal fat intake enhances prostate cancer progression
and reduces glutathione peroxidase 3 expression in early stages of
TRAMP mice. Prostate 2014, 74:1266�1277.
52. Bidoli E, Talamini R, Bosetti C, Negri E, Maruzzi D, Montella M, Franceschi S,
La Vecchia C: Macronutrients, fatty acids, cholesterol and prostate cancer
risk. Ann Oncol 2005, 16:152�157.
53. Park SY, Murphy SP, Wilkens LR, Henderson BE, Kolonel LN: Fat and meat
intake and prostate cancer risk: the multiethnic cohort study. Int J Cancer
2007, 121:1339�1345.
54. Wallstrom P, Bjartell A, Gullberg B, Olsson H, Wirfalt E: A prospective study
on dietary fat and incidence of prostate cancer (Malmo, Sweden).
Cancer Causes Control 2007, 18:1107�1121.
55. Crowe FL, Key TJ, Appleby PN, Travis RC, Overvad K, Jakobsen MU,
Johnsen NF, Tj�nneland A, Linseisen J, Rohrmann S, Boeing H, Pischon T,
Trichopoulou A, Lagiou P, Trichopoulos D, Sacerdote C, Palli D, Tumino R,
Krogh V, Bueno-de-Mesquita HB, Kiemeney LA, Chirlaque MD, Ardanaz E,
S�nchez MJ, Larra�aga N, Gonz�lez CA, Quir�s JR, Manjer J, Wirf�lt E, Stattin
P, et al: Dietary fat intake and risk of prostate cancer in the European
Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 2008,
87:1405�1413.
56. Ohwaki K, Endo F, Kachi Y, Hattori K, Muraishi O, Nishikitani M, Yano E:
Relationship between dietary factors and prostate-specific antigen in
healthy men. Urol Int 2012, 89:270�274.
57. Bassett JK, Severi G, Hodge AM, MacInnis RJ, Gibson RA, Hopper JL,
English DR, Giles GG: Plasma phospholipid fatty acids, dietary fatty acids
and prostate cancer risk. Int J Cancer 2013, 133:1882�1891.
58. Richman EL, Kenfield SA, Chavarro JE, Stampfer MJ, Giovannucci EL, Willett
WC, Chan JM: Fat intake after diagnosis and risk of lethal prostate cancer
and all-cause mortality. JAMA Intern Med 2013, 173:1318�1326.
59. Williams CD, Whitley BM, Hoyo C, Grant DJ, Iraggi JD, Newman KA, Gerber
L, Taylor LA, McKeever MG, Freedland SJ: A high ratio of dietary n-6/n-3
polyunsaturated fatty acids is associated with increased risk of prostate
cancer. Nutr Res 2011, 31:1�8.
60. Chua ME, Sio MC, Sorongon MC, Dy JS: Relationship of dietary intake of
omega-3 and omega-6 fatty acids with risk of prostate cancer
development: a meta-analysis of prospective studies and review of
literature. Prostate Cancer 2012, 2012:826254.
61. Berquin IM, Edwards IJ, Kridel SJ, Chen YQ: Polyunsaturated fatty acid
metabolism in prostate cancer. Cancer Metastasis Rev 2011, 30:295�309.
62. Aronson WJ, Kobayashi N, Barnard RJ, Henning S, Huang M, Jardack PM, Liu
B, Gray A, Wan J, Konijeti R, Freedland SJ, Castor B, Heber D, Elashoff D, Said
J, Cohen P, Galet C: Phase II prospective randomized trial of a low-fat diet
with fish oil supplementation in men undergoing radical prostatectomy.
Cancer Prev Res (Phila) 2011, 4:2062�2071.
63. Hughes-Fulford M, Li CF, Boonyaratanakornkit J, Sayyah S: Arachidonic acid
activates phosphatidylinositol 3-kinase signaling and induces gene
expression in prostate cancer. Cancer Res 2006, 66:1427�1433.
64. Moreel X, Allaire J, Leger C, Caron A, Labonte ME, Lamarche B, Julien P,
Desmeules P, T�tu B, Fradet V: Prostatic and dietary omega-3 fatty acids
and prostate cancer progression during active surveillance. Cancer Prev
Res (Phila) 2014, 7:766�776.
65. Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D,
Steward W, Dennison A: The effect of omega-3 FAs on tumour angiogenesis
and their therapeutic potential. Eur J Cancer 2009, 45:2077�2086.
66. Gu Z, Suburu J, Chen H, Chen YQ: Mechanisms of omega-3 polyunsaturated
fatty acids in prostate cancer prevention. Biomed Res Int 2013, 2013:824563.
67. Lloyd JC, Masko EM, Wu C, Keenan MM, Pilla DM, Aronson WJ, Chi JT,
Freedland SJ: Fish oil slows prostate cancer xenograft growth relative to
other dietary fats and is associated with decreased mitochondrial and
insulin pathway gene expression. Prostate Cancer Prostatic Dis 2013,
16:285�291.
68. Williams CM, Burdge G: Long-chain n-3 PUFA: plant v. marine sources.
Proc Nutr Soc 2006, 65:42�50.
69. Galet C, Gollapudi K, Stepanian S, Byrd JB, Henning SM, Grogan T, Elashoff
D, Heber D, Said J, Cohen P, Aronson WJ: Effect of a low-fat fish oil diet
on proinflammatory eicosanoids and cell-cycle progression score in
men undergoing radical prostatectomy. Cancer Prev Res (Phila) 2014,
7:97�104.
70. Bosire C, Stampfer MJ, Subar AF, Park Y, Kirkpatrick SI, Chiuve SE, Hollenbeck
AR, Reedy J: Index-based dietary patterns and the risk of prostate cancer
in the NIH-AARP diet and health study. Am J Epidemiol 2013, 177:504�513.
71. Aronson WJ, Barnard RJ, Freedland SJ, Henning S, Elashoff D, Jardack PM,
Cohen P, Heber D, Kobayashi N: Growth inhibitory effect of low fat diet
on prostate cancer cells: results of a prospective, randomized dietary
intervention trial in men with prostate cancer. J Urol 2010, 183:345�350.
72. Brouwer IA, Geleijnse JM, Klaasen VM, Smit LA, Giltay EJ, de Goede J,
Heijboer AC, Kromhout D, Katan MB: Effect of alpha linolenic acid
supplementation on serum prostate specific antigen (PSA): results from
the alpha omega trial. PLoS One 2013, 8:e81519.
73. Chua ME, Sio MC, Sorongon MC, Morales ML Jr: The relevance of serum
levels of long chain omega-3 polyunsaturated fatty acids and prostate
cancer risk: A meta-analysis. Can Urol Assoc J 2013, 7:E333�E343.
74. Yue S, Li J, Lee SY, Lee HJ, Shao T, Song B, Cheng L, Masterson TA, Liu X,
Ratliff TL, Cheng JX: Cholesteryl ester accumulation induced by PTEN loss
and PI3K/AKT activation underlies human prostate cancer
aggressiveness. Cell Metab 2014, 19:393�406.

75. Sun Y, Sukumaran P, Varma A, Derry S, Sahmoun AE, Singh BB: Cholesterolinduced
activation of TRPM7 regulates cell proliferation, migration,
and viability of human prostate cells. Biochim Biophys Acta 1843,
2014:1839�1850.
76. Murai T: Cholesterol lowering: role in cancer prevention and treatment.
Biol Chem 2014. doi:10.1515/hsz-2014-0194. [Epub ahead of time]
77. Zhuang L, Kim J, Adam RM, Solomon KR, Freeman MR: Cholesterol
targeting alters lipid raft composition and cell survival in prostate cancer
cells and xenografts. J Clin Invest 2005, 115:959�968.
78. Mostaghel EA, Solomon KR, Pelton K, Freeman MR, Montgomery RB:
Impact of circulating cholesterol levels on growth and intratumoral
androgen concentration of prostate tumors. PLoS One 2012,
7:e30062.
79. Morote J, Celma A, Planas J, Placer J, de Torres I, Olivan M, Carles J,
Revent�s J, Doll A: Role of serum cholesterol and statin use in the risk of
prostate cancer detection and tumor aggressiveness. Int J Mol Sci 2014,
15:13615�13623.
80. Allott EH, Howard LE, Cooperberg MR, Kane CJ, Aronson WJ, Terris MK,
Amling CL, Freedland SJ: Postoperative statin use and risk of biochemical
recurrence following radical prostatectomy: results from the Shared
Equal Access Regional Cancer Hospital (SEARCH) database. BJU Int 2014,
114:661�666.
81. Jespersen CG, Norgaard M, Friis S, Skriver C, Borre M: Statin use and risk of
prostate cancer: A Danish population-based case�control study,
1997�2010. Cancer Epidemiol 2014, 38:42�47.
82. Meyers CD, Kashyap ML: Pharmacologic elevation of high-density
lipoproteins: recent insights on mechanism of action and atherosclerosis
protection. Curr Opin Cardiol 2004, 19:366�373.
83. Xia P, Vadas MA, Rye KA, Barter PJ, Gamble JR: High density lipoproteins
(HDL) interrupt the sphingosine kinase signaling pathway. A possible
mechanism for protection against atherosclerosis by HDL. J Biol Chem
1999, 274:33143�33147.
84. Kotani K, Sekine Y, Ishikawa S, Ikpot IZ, Suzuki K, Remaley AT: High-density
lipoprotein and prostate cancer: an overview. J Epidemiol 2013,
23:313�319.
85. Soni MG, Thurmond TS, Miller ER 3rd, Spriggs T, Bendich A, Omaye ST:
Safety of vitamins and minerals: controversies and perspective. Toxicol
Sci 2010, 118:348�355.
86. Neuhouser ML, Barnett MJ, Kristal AR, Ambrosone CB, King I, Thornquist M,
Goodman G: (n-6) PUFA increase and dairy foods decrease prostate
cancer risk in heavy smokers. J Nutr 2007, 137:1821�1827.
87. Karppi J, Kurl S, Laukkanen JA, Kauhanen J: Serum beta-carotene in relation
to risk of prostate cancer: the Kuopio Ischaemic Heart Disease Risk
Factor study. Nutr Cancer 2012, 64:361�367.
88. Margalit DN, Kasperzyk JL, Martin NE, Sesso HD, Gaziano JM, Ma J, Stampfer
MJ, Mucci LA: Beta-carotene antioxidant use during radiation therapy
and prostate cancer outcome in the Physicians� Health Study. Int J Radiat
Oncol Biol Phys 2012, 83:28�32.
89. Roswall N, Larsen SB, Friis S, Outzen M, Olsen A, Christensen J, Dragsted LO,
Tj�nneland A: Micronutrient intake and risk of prostate cancer in a
cohort of middle-aged, Danish men. Cancer Causes Control 2013,
24:1129�1135.
90. Gilbert R, Metcalfe C, Fraser WD, Donovan J, Hamdy F, Neal DE, Lane JA,
Martin RM: Associations of circulating retinol, vitamin E, and 1,25-
dihydroxyvitamin D with prostate cancer diagnosis, stage, and grade.
Cancer Causes Control 2012, 23:1865�1873.
91. Bistulfi G, Foster BA, Karasik E, Gillard B, Miecznikowski J, Dhiman VK,
Smiraglia DJ: Dietary folate deficiency blocks prostate cancer progression
in the TRAMP model. Cancer Prev Res (Phila) 2011, 4:1825�1834.
92. Collin SM: Folate and B12 in prostate cancer. Adv Clin Chem 2013,
60:1�63.
93. Tio M, Andrici J, Cox MR, Eslick GD: Folate intake and the risk of prostate
cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic
Dis 2014, 17:213�219.
94. Vollset SE, Clarke R, Lewington S, Ebbing M, Halsey J, Lonn E, Armitage J,
Manson JE, Hankey GJ, Spence JD, Galan P, B�naa KH, Jamison R, Gaziano
JM, Guarino P, Baron JA, Logan RF, Giovannucci EL, den Heijer M, Ueland
PM, Bennett D, Collins R, Peto R, B-Vitamin Treatment Trialists’ Collaboration:
Effects of folic acid supplementation on overall and site-specific cancer
incidence during the randomised trials: meta-analyses of data on 50,000
individuals. Lancet 2013, 381:1029�1036.
95. Verhage BA, Cremers P, Schouten LJ, Goldbohm RA, van den Brandt PA:
Dietary folate and folate vitamers and the risk of prostate cancer
in The Netherlands Cohort Study. Cancer Causes Control 2012,
23:2003�2011.
96. Tavani A, Malerba S, Pelucchi C, Dal Maso L, Zucchetto A, Serraino D, Levi F,
Montella M, Franceschi S, Zambon A, La Vecchia C: Dietary folates and
cancer risk in a network of case�control studies. Ann Oncol 2012,
23:2737�2742.
97. Moreira DM, Banez LL, Presti JC Jr, Aronson WJ, Terris MK, Kane CJ, Amling
CL, Freedland SJ: High serum folate is associated with reduced
biochemical recurrence after radical prostatectomy: results from the
SEARCH Database. Int Braz J Urol 2013, 39:312�318. discussion 319.
98. Han YY, Song JY, Talbott EO: Serum folate and prostate-specific antigen in
the United States. Cancer Causes Control 2013, 24:1595�1604.
99. Rycyna KJ, Bacich DJ, O’Keefe DS: Opposing roles of folate in prostate
cancer. Urology 2013, 82:1197�1203.
100. Gilbert R, Martin RM, Beynon R, Harris R, Savovic J, Zuccolo L, Bekkering GE,
Fraser WD, Sterne JA, Metcalfe: Associations of circulating and dietary
vitamin D with prostate cancer risk: a systematic review and dose�
response meta-analysis. Cancer Causes Control 2011, 22:319�340.
101. Schenk JM, Till CA, Tangen CM, Goodman PJ, Song X, Torkko KC, Kristal AR,
Peters U, Neuhouser ML: Serum 25-hydroxyvitamin d concentrations and
risk of prostate cancer: results from the Prostate Cancer Prevention Trial.
Cancer Epidemiol Biomarkers Prev 2014, 23:1484�1493.
102. Schwartz GG: Vitamin D, in blood and risk of prostate cancer: lessons
from the Selenium and Vitamin E Cancer Prevention Trial and the
Prostate Cancer Prevention Trial. Cancer Epidemiol Biomarkers Prev 2014,
23:1447�1449.
103. Giangreco AA, Vaishnav A, Wagner D, Finelli A, Fleshner N, Van der Kwast T,
Vieth R, Nonn L: Tumor suppressor microRNAs, miR-100 and -125b, are
regulated by 1,25-dihydroxyvitamin D in primary prostate cells and in
patient tissue. Cancer Prev Res (Phila) 2013, 6:483�494.
104. Hollis BW, Marshall DT, Savage SJ, Garrett-Mayer E, Kindy MS, Gattoni-Celli S:
Vitamin D3 supplementation, low-risk prostate cancer, and health
disparities. J Steroid Biochem Mol Biol 2013, 136:233�237.
105. Sha J, Pan J, Ping P, Xuan H, Li D, Bo J, Liu D, Huang Y: Synergistic effect
and mechanism of vitamin A and vitamin D on inducing apoptosis of
prostate cancer cells. Mol Biol Rep 2013, 40:2763�2768.
106. Chandler PD, Giovannucci EL, Scott JB, Bennett GG, Ng K, Chan AT, Hollis
BW, Emmons KM, Fuchs CS, Drake BF: Null association between Vitamin D
and PSA levels among black men in a Vitamin D supplementation trial.
Cancer Epidemiol Biomarkers Prev 2014, 23:1944�1947.
107. Skaaby T, Husemoen LL, Thuesen BH, Pisinger C, Jorgensen T, Roswall N,
Larsen SC, Linneberg A: Prospective population-based study of the
association between serum 25-hydroxyvitamin-D levels and the
incidence of specific types of cancer. Cancer Epidemiol Biomarkers Prev
2014, 23:1220�1229.
108. Holt SK, Kolb S, Fu R, Horst R, Feng Z, Stanford JL: Circulating levels of
25-hydroxyvitamin D and prostate cancer prognosis. Cancer Epidemiol
2013, 37:666�670.
109. Wong YY, Hyde Z, McCaul KA, Yeap BB, Golledge J, Hankey GJ, Flicker L:
In older men, lower plasma 25-hydroxyvitamin D is associated with
reduced incidence of prostate, but not colorectal or lung cancer.
PLoS One 2014, 9:e99954.
110. Xu Y, Shao X, Yao Y, Xu L, Chang L, Jiang Z, Lin Z: Positive association
between circulating 25-hydroxyvitamin D levels and prostate cancer risk:
new findings from an updated meta-analysis. J Cancer Res Clin Oncol
2014, 140:1465�1477.
111. Meyer HE, Robsahm TE, Bjorge T, Brustad M, Blomhoff R: Vitamin D, season,
and risk of prostate cancer: a nested case�control study within
Norwegian health studies. Am J Clin Nutr 2013, 97:147�154.
112. Kristal AR, Till C, Song X, Tangen CM, Goodman PJ, Neuhauser ML, Schenk
JM, Thompson IM, Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL,
Klein EA: Plasma vitamin D and prostate cancer risk: results from the
Selenium and Vitamin E Cancer Prevention Trial. Cancer Epidemiol
Biomarkers Prev 2014, 23:1494�1504.
113. Weinstein SJ, Mondul AM, Kopp W, Rager H, Virtamo J, Albanes D:
Circulating 25-hydroxyvitamin D, vitamin D-binding protein and risk of
prostate cancer. Int J Cancer 2013, 132:2940�2947.
114. Guo Z, Wen J, Kan Q, Huang S, Liu X, Sun N, Li Z: Lack of association
between vitamin D receptor gene FokI and BsmI polymorphisms and�prostate cancer risk: an updated meta-analysis involving 21,756 subjects. Tumour Biol 2013, 34:3189�3200115. Wang L, Sesso HD, Glynn RJ, Christen WG, Bubes V, Manson JE, Buring JE,
Gaziano JM: Vitamin E and C supplementation and risk of cancer in men:
posttrial follow-up in the Physicians� Health Study II randomized trial.
Am J Clin Nutr 2014, 100:915�923.
116. Virtamo J, Taylor PR, Kontto J, Mannisto S, Utriainen M, Weinstein SJ,
Huttunen J, Albanes D: Effects of alpha-tocopherol and beta-carotene
supplementation on cancer incidence and mortality: 18-year
postintervention follow-up of the Alpha-tocopherol, Beta-carotene
Cancer Prevention Study. Int J Cancer 2014, 135:178�185.
117. Basu A, Imrhan V: Vitamin E and prostate cancer: is vitamin E succinate a
superior chemopreventive agent? Nutr Rev 2005, 63:247�251.
118. Lawson KA, Wright ME, Subar A, Mouw T, Hollenbeck A, Schatzkin A,
Leitzmann MF: Multivitamin use and risk of prostate cancer in the
National Institutes of Health-AARP Diet and Health Study. J Natl Cancer
Inst 2007, 99:754�764.
119. Calle EE, Rodriguez C, Jacobs EJ, Almon ML, Chao A, McCullough ML,
Feigelson HS, Thun MJ: The American Cancer Society Cancer Prevention
Study II Nutrition Cohort: rationale, study design, and baseline
characteristics. Cancer 2002, 94:2490�2501.
120. Weinstein SJ, Peters U, Ahn J, Friesen MD, Riboli E, Hayes RB, Albanes D:
Serum alpha-tocopherol and gamma-tocopherol concentrations and
prostate cancer risk in the PLCO Screening Trial: a nested case�control
study. PLoS One 2012, 7:e40204.
121. Cui R, Liu ZQ, Xu Q: Blood alpha-tocopherol, gamma-tocopherol levels
and risk of prostate cancer: a meta-analysis of prospective studies.
PLoS One 2014, 9:e93044.
122. Major JM, Yu K, Weinstein SJ, Berndt SI, Hyland PL, Yeager M, Chanock S,
Albanes D: Genetic variants reflecting higher vitamin e status in men are
associated with reduced risk of prostate cancer. J Nutr May 2014,
144:729�733.
123. Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ,
Minasian LM, Ford LG, Parnes HL, Gaziano JM, Karp DD, Lieber MM, Walther
PJ, Klotz L, Parsons JK, Chin JL, Darke AK, Lippman SM, Goodman GE,
Meyskens FL Jr, Baker LH: Vitamin E and the risk of prostate cancer: the
Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011,
306:1549�1556.
124. Albanes D, Till C, Klein EA, Goodman PJ, Mondul AM, Weinstein SJ, aylor PR,
Parnes HL, Gaziano JM, Song X, Fleshner NE, Brown PH, Meyskens FL Jr,
Thompson IM: Plasma tocopherols and risk of prostate cancer in the
Selenium and Vitamin E Cancer Prevention Trial (SELECT). Cancer Prev Res
(Phila) 2014, 7:886�895.
125. Kristal AR, Darke AK, Morris JS, Tangen CM, Goodman PJ, Thompson IM,
Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL, Lippman SM,
Klein EA: Baseline selenium status and effects of selenium and vitamin e
supplementation on prostate cancer risk. J Natl Cancer Inst 2014,
106:djt456.
126. Jamison JM, Gilloteaux J, Taper HS, Summers JL: Evaluation of the in vitro
and in vivo antitumor activities of vitamin C and K-3 combinations
against human prostate cancer. J Nutr 2001, 131:158S�160S.
127. Nimptsch K, Rohrmann S, Kaaks R, Linseisen J: Dietary vitamin K intake
in relation to cancer incidence and mortality: results from the
Heidelberg cohort of the European Prospective Investigation into
Cancer and Nutrition (EPIC-Heidelberg). Am J Clin Nutr 2010,
91:1348�1358.
128. Ma RW, Chapman K: A systematic review of the effect of diet in prostate
cancer prevention and treatment. J Hum Nutr Diet 2009, 22:187�199.
quiz 200�182.
129. Bristow SM, Bolland MJ, MacLennan GS, Avenell A, Grey A, Gamble GD, Reid
IR: Calcium supplements and cancer risk: a meta-analysis of randomised
controlled trials. Br J Nutr 2013, 110:1384�1393.
130. Williams CD, Whitley BM, Hoyo C, Grant DJ, Schwartz GG, Presti JC Jr, Iraggi
JD, Newman KA, Gerber L, Taylor LA, McKeever MG, Freedland SJ: Dietary
calcium and risk for prostate cancer: a case�control study among US
veterans. Prev Chronic Dis 2012, 9:E39.
131. Hori S, Butler E, McLoughlin J: Prostate cancer and diet: food for thought?
BJU Int 2011, 107:1348�1359.
132. Geybels MS, Verhage BA, van Schooten FJ, Goldbohm RA, van den Brandt
PA: Advanced prostate cancer risk in relation to toenail selenium levels.
J Natl Cancer Inst 2013, 105:1394�1401.
133. Singh RP, Agarwal R: Prostate cancer chemoprevention by silibinin: bench
to bedside. Mol Carcinog 2006, 45:436�442.
134. Ting H, Deep G, Agarwal R: Molecular mechanisms of silibinin-mediated
cancer chemoprevention with major emphasis on prostate cancer.
AAPS J 2013, 15:707�716.
135. Ting HJ, Deep G, Jain AK, Cimic A, Sirintrapun J, Romero LM, Cramer SD,
Agarwal C, Agarwal R: Silibinin prevents prostate cancer cell-mediated
differentiation of naive fibroblasts into cancer-associated fibroblast
phenotype by targeting TGF beta2. Mol Carcinog 2014. doi:10.1002/
mc.22135. [Epub ahead of time]
136. Goel A, Aggarwal BB: Curcumin, the golden spice from Indian saffron, is a
chemosensitizer and radiosensitizer for tumors and chemoprotector and
radioprotector for normal organs. Nutr Cancer 2010, 62:919�930.
137. Khan N, Adhami VM, Mukhtar H: Apoptosis by dietary agents for
prevention and treatment of prostate cancer. Endocr Relat Cancer 2010,
17:R39�R52.
138. Heber D: Pomegranate ellagitannins. In Herbal Medicine: Biomolecular and
Clinical Aspects. 2nd edition. Edited by Benzie IF, Wachtel-Galor S. Boca
Raton, FL: CRC Press; 2011.
139. Pantuck AJ, Leppert JT, Zomorodian N, Aronson W, Hong J, Barnard RJ,
Seeram N, Liker H, Wang H, Elashoff R, Heber D, Aviram M, Ignarro L,
Belldegrun A: Phase II study of pomegranate juice for men with rising
prostate-specific antigen following surgery or radiation for prostate
cancer. Clin Cancer Res 2006, 12:4018�4026.
140. Paller CJ, Ye X, Wozniak PJ, Gillespie BK, Sieber PR, Greengold RH, Stockton
BR, Hertzman BL, Efros MD, Roper RP, Liker HR, Carducci MA: A randomized
phase II study of pomegranate extract for men with rising PSA following
initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis
2013, 16:50�55.
141. Freedland SJ, Carducci M, Kroeger N, Partin A, Rao JY, Jin Y, Kerkoutian S,
Wu H, Li Y, Creel P, Mundy K, Gurganus R, Fedor H, King SA, Zhang Y,
Heber D, Pantuck AJ: A double-blind, randomized, neoadjuvant study of
the tissue effects of POMx pills in men with prostate cancer before
radical prostatectomy. Cancer Prev Res (Phila) 2013, 6:1120�1127.
142. Wang P, Aronson WJ, Huang M, Zhang Y, Lee RP, Heber D, Henning SM:
Green tea polyphenols and metabolites in prostatectomy tissue:
implications for cancer prevention. Cancer Prev Res (Phila) 2010,
3:985�993.
143. Kurahashi N, Sasazuki S, Iwasaki M, Inoue M, Tsugane S: Green tea
consumption and prostate cancer risk in Japanese men: a prospective
study. Am J Epidemiol 2008, 167:71�77.
144. McLarty J, Bigelow RL, Smith M, Elmajian D, Ankem M, Cardelli JA: Tea
polyphenols decrease serum levels of prostate-specific antigen,
hepatocyte growth factor, and vascular endothelial growth factor in
prostate cancer patients and inhibit production of hepatocyte growth
factor and vascular endothelial growth factor in vitro. Cancer Prev Res
(Phila) 2009, 2:673�682.
145. Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A:
Chemoprevention of human prostate cancer by oral administration of
green tea catechins in volunteers with high-grade prostate intraepithelial
neoplasia: a preliminary report from a one-year proof-of-principle study.
Cancer Res 2006, 66:1234�1240.
146. Fraser SP, Peters A, Fleming-Jones S, Mukhey D, Djamgoz MB: Resveratrol:
inhibitory effects on metastatic cell behaviors and voltage-gated Na(+)
channel activity in rat prostate cancer in vitro. Nutr Cancer 2014,
66:1047�1058.
147. Oskarsson A, Spatafora C, Tringali C, Andersson AO: Inhibition of CYP17A1
activity by resveratrol, piceatannol, and synthetic resveratrol analogs.
Prostate 2014, 74:839�851.
148. Ferruelo A, Romero I, Cabrera PM, Arance I, Andres G, Angulo JC: Effects of
resveratrol and other wine polyphenols on the proliferation, apoptosis
and androgen receptor expression in LNCaP cells. Actas Urol Esp Jul-Aug
2014, 38:397�404.
149. Osmond GW, Masko EM, Tyler DS, Freedland SJ, Pizzo S: In vitro and in vivo
evaluation of resveratrol and 3,5-dihydroxy-4?-acetoxy-trans-stilbene in
the treatment of human prostate carcinoma and melanoma. J Surg Res
2013, 179:e141�e148.
150. Baur JA, Sinclair DA: Therapeutic potential of resveratrol: the in vivo
evidence. Nat Rev Drug Discov 2006, 5:493�506.
151. Klink JC, Tewari AK, Masko EM, Antonelli J, Febbo PG, Cohen P, Dewhirst
MW, Pizzo SV, Freedland SJ: Resveratrol worsens survival in SCID mice with prostate cancer xenografts in a cell-line specific manner, through paradoxical effects on oncogenic pathways. Prostate 2013, 73:754�762.

152. Huang EC, Zhao Y, Chen G, Baek SJ, McEntee MF, Minkin S, Biggerstaff JP,
Whelan J: Zyflamend, a polyherbal mixture, down regulates class I and
class II histone deacetylases and increases p21 levels in castrate-resistant
prostate cancer cells. BMC Complement Altern Med 2014, 14:68.
153. Huang EC, McEntee MF, Whelan J: Zyflamend, a combination of herbal
extracts, attenuates tumor growth in murine xenograft models of
prostate cancer. Nutr Cancer 2012, 64:749�760.
154. Yan J, Xie B, Capodice JL, Katz AE: Zyflamend inhibits the expression and
function of androgen receptor and acts synergistically with bicalutimide
to inhibit prostate cancer cell growth. Prostate 2012, 72:244�252.
155. Kunnumakkara AB, Sung B, Ravindran J, Diagaradjane P, Deorukhkar A, Dey
S, Koca C, Tong Z, Gelovani JG, Guha S, Krishnan S, Aggarwal BB: Zyflamend
suppresses growth and sensitizes human pancreatic tumors to
gemcitabine in an orthotopic mouse model through modulation of
multiple targets. Int J Cancer 2012, 131:E292�E303.
156. Capodice JL, Gorroochurn P, Cammack AS, Eric G, McKiernan JM, Benson
MC, Stone BA, Katz AE: Zyflamend in men with high-grade prostatic
intraepithelial neoplasia: results of a phase I clinical trial. J Soc Integr
Oncol 2009, 7:43�51.
157. Rafailov S, Cammack S, Stone BA, Katz AE: The role of Zyflamend, an
herbal anti-inflammatory, as a potential chemopreventive agent against
prostate cancer: a case report. Integr Cancer Ther 2007, 6:74�76.
158. Askari F, Parizi MK, Jessri M, Rashidkhani B: Fruit and vegetable intake in
relation to prostate cancer in Iranian men: a case�control study.
Asian Pac J Cancer Prev 2014, 15:5223�5227.
159. Liu B, Mao Q, Cao M, Xie L: Cruciferous vegetables intake and risk of
prostate cancer: a meta-analysis. Int J Urol 2012, 19:134�141.
160. Richman EL, Carroll PR, Chan JM: Vegetable and fruit intake after
diagnosis and risk of prostate cancer progression. Int J Cancer 2012,
131:201�210.
161. Hsing AW, Chokkalingam AP, Gao YT, Madigan MP, Deng J, Gridley G,
Fraumeni JF Jr: Allium vegetables and risk of prostate cancer: a
population-based study. J Natl Cancer Inst 2002, 94:1648�1651.
162. Chan R, Lok K, Woo J: Prostate cancer and vegetable consumption.
Mol Nutr Food Res 2009, 53:201�216.
163. Thomas R, Williams M, Sharma H, Chaudry A, Bellamy P: A double-blind,
placebo-controlled randomised trial evaluating the effect of a
polyphenol-rich whole food supplement on PSA progression in men
with prostate cancer-the UK NCRN Pomi-T study. Prostate Cancer Prostatic
Dis 2014, 17:180�186.
164. Yang CM, Lu IH, Chen HY, Hu ML: Lycopene inhibits the proliferation of
androgen-dependent human prostate tumor cells through activation of
PPARgamma-LXRalpha-ABCA1 pathway. J Nutr Biochem 2012, 23:8�17.
165. Qiu X, Yuan Y, Vaishnav A, Tessel MA, Nonn L, van Breemen RB: Effects of
lycopene on protein expression in human primary prostatic epithelial
cells. Cancer Prev Res (Phila) 2013, 6:419�427.
166. Boileau TW, Liao Z, Kim S, Lemeshow S, Erdman JW Jr, Clinton SK: Prostate
carcinogenesis in N-methyl-N-nitrosourea (NMU)-testosterone-treated
rats fed tomato powder, lycopene, or energy-restricted diets. J Natl
Cancer Inst 2003, 95:1578�1586.
167. Konijeti R, Henning S, Moro A, Sheikh A, Elashoff D, Shapiro A, Ku M,
Said JW, Heber D, Cohen P, Aronson WJ: Chemoprevention of prostate
cancer with lycopene in the TRAMP model. Prostate 2010, 70:1547�1554.
168. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC: A prospective
study of tomato products, lycopene, and prostate cancer risk. J Natl
Cancer Inst 2002, 94:391�398.
169. Zu K, Mucci L, Rosner BA, Clinton SK, Loda M, Stampfer MJ, Giovannucci E:
Dietary lycopene, angiogenesis, and prostate cancer: a prospective
study in the prostate-specific antigen era. J Natl Cancer Inst 2014,
106:djt430.
170. Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM, Hennekens CH, Stampfer
MJ: Lower prostate cancer risk in men with elevated plasma lycopene
levels: results of a prospective analysis. Cancer Res 1999, 59:1225�1230.
171. Kristal AR, Till C, Platz EA, Song X, King IB, Neuhouser ML, Ambrosone CB,
Thompson IM: Serum lycopene concentration and prostate cancer risk:
results from the Prostate Cancer Prevention Trial. Cancer Epidemiol
Biomarkers Prev 2011, 20:638�646.
172. Kirsh VA, Mayne ST, Peters U, Chatterjee N, Leitzmann MF, Dixon LB, Urban
DA, Crawford ED, Hayes RB: A prospective study of lycopene and tomato
product intake and risk of prostate cancer. Cancer Epidemiol Biomarkers
Prev 2006, 15:92�98.
173. Mariani S, Lionetto L, Cavallari M, Tubaro A, Rasio D, De Nunzio C, Hong
GM, Borro M, Simmaco M: Low prostate concentration of lycopene is
associated with development of prostate cancer in patients with highgrade
prostatic intraepithelial neoplasia. Int J Mol Sci 2014, 15:1433�1440.
174. Kucuk O, Sarkar FH, Djuric Z, Sakr W, Pollak MN, Khachik F, Banerjee M,
Bertram JS, Wood DP Jr: Effects of lycopene supplementation in patients
with localized prostate cancer. Exp Biol Med (Maywood) 2002, 227:881�885.
175. Chen L, Stacewicz-Sapuntzakis M, Duncan C, Sharifi R, Ghosh L, van
Breemen R, Ashton D, Bowen PE: Oxidative DNA damage in prostate
cancer patients consuming tomato sauce-based entrees as a whole-food
intervention. J Natl Cancer Inst 2001, 93:1872�1879.
176. van Breemen RB, Sharifi R, Viana M, Pajkovic N, Zhu D, Yuan L, Yang Y,
Bowen PE, Stacewicz-Sapuntzakis M: Antioxidant effects of lycopene in
African American men with prostate cancer or benign prostate hyperplasia:
a randomized, controlled trial. Cancer Prev Res (Phila) 2011, 4:711�718.
177. Shafique K, McLoone P, Qureshi K, Leung H, Hart C, Morrison DS: Coffee
consumption and prostate cancer risk: further evidence for inverse
relationship. Nutr J 2012, 11:42.
178. Wilson KM, Kasperzyk JL, Rider JR, Kenfield S, van Dam RM, Stampfer MJ,
Giovannucci E, Mucci LA: Coffee consumption and prostate cancer risk
and progression in the Health Professionals Follow-up Study. J Natl
Cancer Inst 2011, 103:876�884.
179. Bosire C, Stampfer MJ, Subar AF, Wilson KM, Park Y, Sinha R: Coffee
consumption and the risk of overall and fatal prostate cancer in the
NIH-AARP Diet and Health Study. Cancer Causes Control 2013, 24:1527�1534.
180. Arab L, Su LJ, Steck SE, Ang A, Fontham ET, Bensen JT, Mohler JL: Coffee
consumption and prostate cancer aggressiveness among African and
Caucasian Americans in a population-based study. Nutr Cancer 2012,
64:637�642.
181. Phillips RL, Snowdon DA: Association of meat and coffee use with cancers
of the large bowel, breast, and prostate among Seventh-Day Adventists:
preliminary results. Cancer Res 1983, 43:2403 s�2408s.
182. Hsing AW, McLaughlin JK, Schuman LM, Bjelke E, Gridley G, Wacholder S,
Chien HT, Blot WJ: Diet, tobacco use, and fatal prostate cancer: results
from the Lutheran Brotherhood Cohort Study. Cancer Res 1990,
50:6836�6840.
183. Cao S, Liu L, Yin X, Wang Y, Liu J, Lu Z: Coffee consumption and risk of
prostate cancer: a meta-analysis of prospective cohort studies.
Carcinogenesis 2014, 35:256�261.
184. Nordmann AJ, Suter-Zimmermann K, Bucher HC, Shai I, Tuttle KR,
Estruch R, Briel M: Meta-analysis comparing Mediterranean to low-fat
diets for modification of cardiovascular risk factors. Am J Med 2011,
124:841�851. e842.
185. Kapiszewska M: A vegetable to meat consumption ratio as a relevant
factor determining cancer preventive diet. The Mediterranean versus
other European countries. Forum Nutr 2006, 59:130�153.
186. Kenfield SA, Dupre N, Richman EL, Stampfer MJ, Chan JM, Giovannucci EL:
Mediterranean diet and prostate cancer risk and mortality in the Health
Professionals Follow-up Study. Eur Urol 2014, 65:887�894.
187. Ambrosini GL, Fritschi L, de Klerk NH, Mackerras D, Leavy J: Dietary patterns
identified using factor analysis and prostate cancer risk: a case control
study in Western Australia. Ann Epidemiol 2008, 18:364�370.
188. Baade PD, Youlden DR, Krnjacki LJ: International epidemiology of prostate
cancer: geographical distribution and secular trends. Mol Nutr Food Res
2009, 53:171�184.
189. Muller DC, Severi G, Baglietto L, Krishnan K, English DR, Hopper JL, Giles GG:
Dietary patterns and prostate cancer risk. Cancer Epidemiol Biomarkers Prev
2009, 18:3126�3129.
190. Tseng M, Breslow RA, DeVellis RF, Ziegler RG: Dietary patterns and prostate
cancer risk in the National Health and Nutrition Examination Survey
Epidemiological Follow-up Study cohort. Cancer Epidemiol Biomarkers Prev
2004, 13:71�77.
191. Wu K, Hu FB, Willett WC, Giovannucci E: Dietary patterns and risk of
prostate cancer in U.S. men. Cancer Epidemiol Biomarkers Prev 2006,
15:167�171.
192. Daubenmier JJ, Weidner G, Marlin R, Crutchfield L, Dunn-Emke S, Chi C,
Gao B, Carroll P, Ornish D: Lifestyle and health-related quality of life of
men with prostate cancer managed with active surveillance. Urology
2006, 67:125�130.

193. Parsons JK, Newman VA, Mohler JL, Pierce JP, Flatt S, Marshall J: Dietary
modification in patients with prostate cancer on active surveillance: a
randomized, multicentre feasibility study. BJU Int 2008, 101:1227�1231.
194. Mosher CE, Sloane R, Morey MC, Snyder DC, Cohen HJ, Miller PE,
Demark-Wahnefried W: Associations between lifestyle factors and quality
of life among older long-term breast, prostate, and colorectal cancer
survivors. Cancer 2009, 115:4001�4009.
195. Bhindi B, Locke J, Alibhai SM, Kulkarni GS, Margel DS, Hamilton RJ, Finelli A,
Trachtenberg J, Zlotta AR, Toi A, Hersey KM, Evans A, van der Kwast TH,
Fleshner NE: Dissecting the association between metabolic syndrome
and prostate cancer risk: analysis of a large clinical cohort. Eur Urol 2014.
doi:10.1016/j.eururo.2014.01.040. [Epub ahead of time]
196. Esposito K, Chiodini P, Capuano A, Bellastella G, Maiorino MI, Parretta E,
Lenzi A, Giugliano D: Effect of metabolic syndrome and its components
on prostate cancer risk: meta-analysis. J Endocrinol Invest 2013,
36:132�139.
197. U.S. Department of Agriculture and U.S. Department of Health and
Human Services. Dietary Guidelines for Americans, 2010. 7th edition.
Washington, DC: U.S. Government Printing Office, December, 2010.

Close Accordion

Cancer: A Preventable Disease

Cancer: A Preventable Disease

Cancer:�Abstract

This year, more than 1 million Americans and more than 10 million people worldwide are expected to be diagnosed with cancer, a disease commonly believed to be preventable. Only 5�10% of all cancer cases can be attributed to genetic defects, whereas the remaining 90�95% have their roots in the environment and lifestyle. The lifestyle factors include cigarette smoking, diet (fried foods, red meat), alcohol, sun exposure, environmental pollutants, infections, stress, obesity, and physical inactivity. The evidence indicates that of all cancer-related deaths, almost 25�30% are due to tobacco, as many as 30� 35% are linked to diet, about 15�20% are due to infections, and the remaining percentage are due to other factors like radiation, stress, physical activity, environmental pollutants etc. Therefore, cancer prevention requires smoking cessation, increased ingestion of fruits and vegetables, moderate use of alcohol, caloric restriction, exercise, avoidance of direct exposure to sunlight, minimal meat consumption, use of whole grains, use of vaccinations, and regular check-ups. In this review, we present evidence that inflammation is the link between the agents/factors that cause cancer and the agents that prevent it. In addition, we provide evidence that cancer is a preventable disease that requires major lifestyle changes.

KEY WORDS: cancer; environmental risk factors; genetic risk factors; prevention.

INTRODUCTION

After sequencing his own genome, pioneer genomic researcher Craig Venter remarked at a leadership for the twenty-first century conference, �Human biology is actually far more complicated than we imagine. Everybody talks about the genes that they received from their mother and father, for this trait or the other. But in reality, those genes have very little impact on life outcomes. Our biology is way too complicated for that and deals with hundreds of thousands of independent factors. Genes are absolutely not our fate. They can give us useful information about the increased risk of a disease, but in most cases they will not determine the actual cause of the disease, or the actual incidence of somebody getting it. Most biology will come from the complex interaction of all the proteins and cells working with environmental factors, not driven directly by the genetic code� (http://indiatoday.digitalto day.in/index.php?option=com_content&task=view&isseid= 48&id=6022&sectionid=30&Itemid=1).

This statement is very important because looking to the human genome for solutions to most chronic illnesses, including the diagnosis, prevention, and treatment of cancer, is overemphasized in today�s world. Observational studies, however, have indicated that as we migrate from one country to another, our chances of being diagnosed with most chronic illnesses are determined not by the country we come from but by the country we migrate to (1�4). In addition, studies with identical twins have suggested that genes are not the source of most chronic illnesses. For instance, the concordance between identical twins for breast cancer was found to be only 20% (5). Instead of our genes, our lifestyle and environment account for 90�95% of our most chronic illnesses.

Cancer continues to be a worldwide killer, despite the enormous amount of research and rapid developments seen during the past decade. According to recent statistics, cancer accounts for about 23% of the total deaths in the USA and is the second most common cause of death after heart disease (6). Death rates for heart disease, however, have been steeply decreasing in both older and younger populations in the USA from 1975 through 2002. In contrast, no appreciable differences in death rates for cancer have been observed in the United States (6).

By 2020, the world population is expected to have increased to 7.5 billion; of this number, approximately 15 million new cancer cases will be diagnosed, and 12 million cancer patients will die (7). These trends of cancer incidence and death rates again remind us of Dr. John Bailer�s May 1985 judgment of the US national cancer program as a �qualified failure,� a judgment made 14 years after President Nixon�s official declaration of the �War on Cancer.� Even after an additional quarter century of extensive research, researchers are still trying to determine whether cancer is preventable and are asking �If it is preventable, why are we losing the war on cancer?� In this review, we attempt to answer this question by analyzing the potential risk factors of cancer and explore our options for modulating these risk factors.

Cancer is caused by both internal factors (such as inherited mutations, hormones, and immune conditions) and environmental/acquired factors (such as tobacco, diet, radiation, and infectious organisms; Fig. 1). The link between diet and cancer is revealed by the large variation in rates of specific cancers in various countries and by the observed changes in the incidence of cancer in migrating. For example, Asians have been shown to have a 25 times lower incidence of prostate cancer and a ten times lower incidence of breast cancer than do residents of Western countries, and the rates for these cancers increase substantially after Asians migrate to the West (http://www.dietandcancerreportorg/?p=ER).

The importance of lifestyle factors in the development of cancer was also shown in studies of monozygotic twins (8). Only 5�10% of all cancers are due to an inherited gene defect. Various cancers that have been linked to genetic defects are shown in Fig. 2. Although all cancers are a result of multiple mutations (9, 10), these mutations are due to interaction with the environment (11, 12).

These observations indicate that most cancers are not of hereditary origin and that lifestyle factors, such as dietary habits, smoking, alcohol consumption, and infections, have a profound influence on their development (13). Although the hereditary factors cannot be modified, the lifestyle and environmental factors are potentially modifiable. The lesser hereditary influence of cancer and the modifiable nature of the environmental factors point to the preventability of cancer. The important lifestyle factors that affect the incidence and mortality of cancer include tobacco, alcohol, diet, obesity, infectious agents, environmental pollutants, and radiation.

RISK FACTORS OF CANCER: Tobacco

Smoking was identified in 1964 as the primary cause of lung cancer in the US Surgeon General�s Advisory Commission Report (http://profiles.nlm.nih.gov/NN/Views/Alpha Chron/date/10006/05/01/2008), and ever since, efforts have been ongoing to reduce tobacco use. Tobacco use increases the risk of developing at least 14 types of cancer (Fig. 3). In addition, it accounts for about 25�30% of all deaths from cancer and 87% of deaths from lung cancer. Compared with nonsmokers, male smokers are 23 times and female smokers 17 times more likely to develop lung cancer. (http://www. cancer.org/docroot/STT/content/STT_1x_Cancer_Facts_and_ Figures_2008.asp accessed on 05/01/2008)

The carcinogenic effects of active smoking are well documented; the U. S. Environmental Protection Agency, for example, in 1993 classified environmental tobacco smoke (from passive smoking) as a known (Group A) human lung carcinogen (http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=2835 accessed on 05/01/2008). Tobacco contains at least 50 carcinogens. For example, one tobacco metabolite, benzopyrenediol epoxide, has a direct etiologic association with lung cancer (14). Among all developed countries considered in total, the prevalence of smoking has been slowly declining; however, in the developing countries where 85% of the world�s population resides, the prevalence of smoking is increasing. According to studies of recent trends in tobacco usage, developing countries will consume 71% of the world�s tobacco by 2010, with 80% increased usage projected for East Asia (http://www.fao.org/DOCREP/006/Y4956E/Y4956E00. HTM accessed on 01/11/08). The use of accelerated tobacco- control programs, with an emphasis in areas where usage is increasing, will be the only way to reduce the rates of tobacco-related cancer mortality.

How smoking contributes to cancer is not fully understood. We do know that smoking can alter a large number of cell- signaling pathways. Results from studies in our group have established a link between cigarette smoke and inflammation. Specifically, we showed that tobacco smoke can induce activation of NF-?B, an inflammatory marker (15,16). Thus, anti- inflammatory agents that can suppress NF-?B activation may have potential applications against cigarette smoke.

We also showed that curcumin, derived from the dietary spice turmeric, can block the NF-?B induced by cigarette smoke (15). In addition to curcumin, we discovered that several natural phytochemicals also inhibit the NF-?B induced by various carcinogens (17). Thus, the carcinogenic effects of tobacco appear to be reduced by these dietary agents. A more detailed discussion of dietary agents that can block inflammation and thereby provide chemopreventive effects is presented in the following section.

Alcohol

The first report of the association between alcohol and an increased risk of esophageal cancer was published in 1910 (18). Since then, a number of studies have revealed that chronic alcohol consumption is a risk factor for cancers of the upper aerodigestive tract, including cancers of the oral cavity, pharynx, hypopharynx, larynx, and esophagus (18�21), as well as for cancers of the liver, pancreas, mouth, and breast (Fig. 3). Williams and Horn (22), for example, reported an increased risk of breast cancer due to alcohol. In addition, a collaborative group who studied hormonal factors in breast cancer published their findings from a reanalysis of more than 80% of individual epidemiological studies that had been conducted worldwide on the association between alcohol and breast cancer risk in women. Their analysis showed a 7.1% increase in relative risk of breast cancer for each additional 10 g/day intake of alcohol (23). In another study, Longnecker et al., (24) showed that 4% of all newly diagnosed cases of breast cancer in the USA are due to alcohol use. In addition to it being a risk factor for breast cancer, heavy intake of alcohol (more than 50�70 g/day) is a well-established risk factor for liver (25) and colorectal (26,27) cancers.

There is also evidence of a synergistic effect between heavy alcohol ingestion and hepatitis C virus (HCV) or hepatitis B virus (HBV), which presumably increases the risk of hepatocellular carcinoma (HCC) by more actively promoting cirrhosis. For example, Donato et al. (28) reported that among alcohol drinkers, HCC risk increased linearly with a daily intake of more than 60 g. However, with the concomitant presence of HCV infection, the risk of HCC was two times greater than that observed with alcohol use alone (i.e., a positive synergistic effect). The relationship between alcohol and inflammation has also been well established, especially in terms of alcohol-induced inflammation of the liver.

How alcohol contributes to carcinogenesis is not fully understood but ethanol may play a role. Study findings suggest that ethanol is not a carcinogen but is a cocarcinogen (29). Specifically, when ethanol is metabolized, acetaldehyde and free radicals are generated; free radicals are believed to be predominantly responsible for alcohol-associated carcinogenesis through their binding to DNA and proteins, which destroys folate and results in secondary hyperproliferation. Other mechanisms by which alcohol stimulates carcinogenesis include the induction of cytochrome P-4502E1, which is associated with enhanced production of free radicals and enhanced activation of various procarcinogens present in alcoholic beverages; a change in metabolism and in the distribution of carcinogens, in association with tobacco smoke and diet; alterations in cell-cycle behavior such as cell-cycle duration leading to hyperproliferation; nutritional deficiencies, for example, of methyl, vitamin E, folate, pyridoxal phosphate, zinc, and selenium; and alterations of the immune system. Tissue injury, such as that occurring with cirrhosis of the liver, is a major prerequisite to HCC. In addition, alcohol can activate the NF-?B proinflammatory pathway (30), which can also contribute to tumorigenesis (31). Furthermore, it has been shown that benzopyrene, a cigarette smoke carcinogen, can penetrate the esophagus when combined with ethanol (32). Thus anti-inflammatory agents may be effective for the treatment of alcohol-induced toxicity.

In the upper aerodigestive tract, 25�68% of cancers are attributable to alcohol, and up to 80% of these tumors can be prevented by abstaining from alcohol and smoking (33). Globally, the attributable fraction of cancer deaths due to alcohol drinking is reported to be 3.5% (34). The number of deaths from cancers known to be related to alcohol consumption in the USA could be as low as 6% (as in Utah) or as high as 28% (as in Puerto Rico). These numbers vary from country to country, and in France have approached 20% in males (18).

Diet

In 1981, Doll and Peto (21) estimated that approximately 30�35% of cancer deaths in the USA were linked to diet (Fig. 4). The extent to which diet contributes to cancer deaths varies a great deal, according to the type of cancer (35). For example, diet is linked to cancer deaths in as many as 70% of colorectal cancer cases. How diet contributes to cancer is not fully understood. Most carcinogens that are ingested, such as nitrates, nitrosamines, pesticides, and dioxins, come from food or food additives or from cooking.

Heavy consumption of red meat is a risk factor for several cancers, especially for those of the gastrointestinal tract, but also for colorectal (36�38), prostate (39), bladder (40), breast (41), gastric (42), pancreatic, and oral (43) cancers. Although a study by Dosil-Diaz et al., (44) showed that meat consumption reduced the risk of lung cancer, such consumption is commonly regarded as a risk for cancer for the following reasons. The heterocyclic amines produced during the cooking of meat are carcinogens. Charcoal cooking and/or smoke curing of meat produces harmful carbon compounds such as pyrolysates and amino acids, which have a strong cancerous effect. For instance, PhIP (2-amino-1- methyl-6-phenyl-imidazo[4,5-b]pyridine) is the most abundant mutagen by mass in cooked beef and is responsible for ~20% of the total mutagenicity found in fried beef. Daily intake of PhIP among Americans is estimated to be 280� 460 ng/day per person (45).

Nitrites and nitrates are used in meat because they bind to myoglobin, inhibiting botulinum exotoxin production; however, they are powerful carcinogens (46). Long-term exposure to food additives such as nitrite preservatives and azo dyes has been associated with the induction of carcinogenesis (47). Furthermore, bisphenol from plastic food containers can migrate into food and may increase the risk of breast (48) and prostate (49) cancers. Ingestion of arsenic may increase the risk of bladder, kidney, liver, and lung cancers (50). Saturated fatty acids, trans fatty acids, and refined sugars and flour present in most foods have also been associated with various cancers. Several food carcinogens have been shown to activate inflammatory pathways.

Obesity

According to an American Cancer Society study (51), obesity has been associated with increased mortality from cancers of the colon, breast (in postmenopausal women), endometrium, kidneys (renal cell), esophagus (adenocarcinoma), gastric cardia, pancreas, prostate, gallbladder, and liver (Fig. 5). Findings from this study suggest that of all deaths from cancer in the United States, 14% in men and 20% in women are attributable to excess weight or obesity. Increased modernization and a Westernized diet and lifestyle have been associated with an increased prevalence of overweight people in many developing countries (52).

Studies have shown that the common denominators between obesity and cancer include neurochemicals; hormones such as insulin like growth factor 1 (IGF-1), insulin, leptin; sex steroids; adiposity; insulin resistance; and inflammation (53).

Involvement of signaling pathways such as the IGF/ insulin/Akt signaling pathway, the leptin/JAK/STAT pathway, and other inflammatory cascades have also been linked with both obesity and cancer (53). For instance, hyperglycemia, has been shown to activate NF-?B (54), which could link obesity with cancer. Also known to activate NF-?B are several cytokines produced by adipocytes, such as leptin, tumor necrosis factor (TNF), and interleukin-1 (IL-1) (55). Energy balance and carcinogenesis has been closely linked (53). However, whether inhibitors of these signaling cascades can reduce obesity-related cancer risk remains unanswered. Because of the involvement of multiple signaling pathways, a potential multitargeting agent will likely be needed to reduce obesity-related cancer risk.

Infectious Agents

Worldwide, an estimated 17.8% of neoplasms are associated with infections; this percentage ranges from less than 10% in high-income countries to 25% in African countries (56, 57). Viruses account for most infection-caused cancers (Fig. 6). Human papillomavirus, Epstein Barr virus, Kaposi�s sarcoma- associated herpes virus, human T-lymphotropic virus 1, HIV, HBV, and HCV are associated with risks for cervical cancer, anogenital cancer, skin cancer, nasopharyngeal cancer, Bur- kitt�s lymphoma, Hodgkin�s lymphoma, Kaposi�s sarcoma, adult T-cell leukemia, B-cell lymphoma, and liver cancer.

In Western developed countries, human papillomavirus and HBV are the most frequently encountered oncogenic DNA viruses. Human papillomavirus is directly mutagenic by inducing the viral genes E6 and E7 (58), whereas HBV is believed to be indirectly mutagenic by generating reactive oxygen species through chronic inflammation (59�61). Human T-lymphotropic virus is directly mutagenic, whereas HCV (like HBV) is believed to produce oxidative stress in infected cells and thus to act indirectly through chronic inflammation (62, 63). However, other microorganisms, including selected parasites such as Opisthorchis viverrini or Schistosoma haematobium and bacteria such as Helicobacter pylori, may also be involved, acting as cofactors and/or carcinogens (64).

The mechanisms by which infectious agents promote cancer are becoming increasingly evident. Infection-related inflammation is the major risk factor for cancer, and almost all viruses linked to cancer have been shown to activate the inflammatory marker, NF-?B (65). Similarly, components of Helicobacter pylori have been shown to activate NF-?B (66). Thus, agents that can block chronic inflammation should be effective in treating these conditions.

Environmental Pollution

Environmental pollution has been linked to various cancers (Fig. 7). It includes outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons (PAHs); indoor air pollution by environmental tobacco smoke, formaldehyde, and volatile organic compounds such as benzene and 1,3-butadiene (which may particularly affect children); food pollution by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins, and other organochlorines; carcinogenic metals and metalloids; pharmaceutical medicines; and cosmetics (64).

Numerous outdoor air pollutants such as PAHs increase the risk of cancers, especially lung cancer. PAHs can adhere to fine carbon particles in the atmosphere and thus penetrate our bodies primarily through breathing. Long-term exposure to PAH-containing air in polluted cities was found to increase the risk of lung cancer deaths. Aside from PAHs and other fine carbon particles, another environmental pollutant, nitric oxide, was found to increase the risk of lung cancer in a European population of nonsmokers. Other studies have shown that nitric oxide can induce lung cancer and promote metastasis. The increased risk of childhood leukemia associated with exposure to motor vehicle exhaust was also reported (64).

Indoor air pollutants such as volatile organic compounds and pesticides increase the risk of childhood leukemia and lymphoma, and children as well as adults exposed to pesticides have increased risk of brain tumors, Wilm�s tumors, Ewing�s sarcoma, and germ cell tumors. In utero exposure to environmental organic pollutants was found to increase the risk for testicular cancer. In addition, dioxan, an environmental pollutant from incinerators, was found to increase the risk of sarcoma and lymphoma.

Long-term exposure to chlorinated drinking water has been associated with increased risk of cancer. Nitrates, in drinking water, can transform to mutagenic N-nitroso compounds, which increase the risk of lymphoma, leukemia, colorectal cancer, and bladder cancer (64).

Radiation

Up to 10% of total cancer cases may be induced by radiation (64), both ionizing and nonionizing, typically from radioactive substances and ultraviolet (UV), pulsed electro- magnetic fields. Cancers induced by radiation include some types of leukemia, lymphoma, thyroid cancers, skin cancers, sarcomas, lung and breast carcinomas. One of the best examples of increased risk of cancer after exposure to radiation is the increased incidence of total malignancies observed in Sweden after exposure to radioactive fallout from the Chernobyl nuclear power plant. Radon and radon decay products in the home and/or at workplaces (such as mines) are the most common sources of exposure to ionizing radiation. The presence of radioactive nuclei from radon, radium, and uranium was found to increase the risk of gastric cancer in rats. Another source of radiation exposure is x-rays used in medical settings for diagnostic or therapeutic purposes. In fact, the risk of breast cancer from x-rays is highest among girls exposed to chest irradiation at puberty, a time of intense breast development. Other factors associated with radiation-induced cancers in humans are patient age and physiological state, synergistic interactions between radiation and carcinogens, and genetic susceptibility toward radiation.

Nonionizing radiation derived primarily from sunlight includes UV rays, which are carcinogenic to humans. Exposure to UV radiation is a major risk for various types of skin cancers including basal cell carcinoma, squamous cell carcinoma, and melanoma. Along with UV exposure from sunlight, UV exposure from sunbeds for cosmetic tanning may account for the growing incidence of melanoma. Depletion of the ozone layer in the stratosphere can augment the dose-intensity of UVB and UVC, which can further increase the incidence of skin cancer.

Low-frequency electromagnetic fields can cause clasto- genic DNA damage. The sources of electromagnetic field exposure are high-voltage power lines, transformers, electric train engines, and more generally, all types of electrical equipments. An increased risk of cancers such as childhood leukemia, brain tumors and breast cancer has been attributed to electromagnetic field exposure. For instance, children living within 200 m of high-voltage power lines have a relative risk of leukemia of 69%, whereas those living between 200 and 600 m from these power lines have a relative risk of 23%. In addition, a recent meta-analysis of all available epidemi- ologic data showed that daily prolonged use of mobile phones for 10 years or more showed a consistent pattern of an increased risk of brain tumors (64).

PREVENTION OF CANCER

The fact that only 5�10% of all cancer cases are due to genetic defects and that the remaining 90�95% are due to environment and lifestyle provides major opportunities for preventing cancer. Because tobacco, diet, infection, obesity, and other factors contribute approximately 25�30%, 30�35%, 15�20%, 10�20%, and 10�15%, respectively, to the incidence of all cancer deaths in the USA, it is clear how we can prevent cancer. Almost 90% of patients diagnosed with lung cancer are cigarette smokers; and cigarette smoking combined with alcohol intake can synergistically contribute to tumorigenesis. Similarly, smokeless tobacco is responsible for 400,000 cases (4% of all cancers) of oral cancer worldwide. Thus avoidance of tobacco products and minimization of alcohol consumption would likely have a major effect on cancer incidence.

Infection by various bacteria and viruses (Fig. 6) is another very prominent cause of various cancers. Vaccines for cervical cancer and HCC should help prevent some of these cancers, and a cleaner environment and modified lifestyle behavior would be even more helpful in preventing infection- caused cancers.

The first FDA approved chemopreventive agent was tamoxifen, for reducing the risk of breast cancer. This agent was found to reduce the breast cancer incidence by 50% in women at high risk. With tamoxifen, there is an increased risk of serious side effects such as uterine cancer, blood clots, ocular disturbances, hypercalcemia, and stroke (http://www.fda.gov/ cder/foi/appletter/1998/17970s40.pdf). Recently it has been shown that a osteoporosis drug raloxifene is as effective as tamoxifen in preventing estrogen-receptor-positive, invasive breast cancer but had fewer side effects than tamoxifen. Though it is better than tamoxifen with respect to side effects, it can cause blood clots and stroke. Other potential side effects of raloxifene include hot flashes, leg cramps, swelling of the legs and feet, flu-like symptoms, joint pain, and sweating (http://www.fda.gov/bbs/topics/NEWS/2007/NEW01698.html).

The second chemopreventive agent to reach to clinic was finasteride, for prostate cancer, which was found to reduce incidence by 25% in men at high risk. The recognized side effects of this agent include erectile dysfunction, lowered sexual desire, impotence and gynecomastia (http://www. cancer.org/docroot/cri/content/cri_2_4_2x_can_prostate_can cer_be_prevented_36.asp). Celecoxib, a COX-2 inhibitor is another approved agent for prevention of familial adenomatous polyposis (FAP). However, the chemopreventive benefit of celecoxib is at the cost of its serious cardiovascular harm (http://www.fda.gov/cder/drug/infopage/cox2/NSAIDdecision Memo.pdf).

The serious side effects of the FDA approved chemopreventive drugs is an issue of particular concern when considering long-term administration of a drug to healthy people who may or may not develop cancer. This clearly indicates the need for agents, which are safe and efficacious in preventing cancer. Diet derived natural products will be potential candidates for this purpose. Diet, obesity, and metabolic syndrome are very much linked to various cancers and may account for as much as 30� 35% of cancer deaths, indicating that a reasonably good fraction of cancer deaths can be prevented by modifying the diet. Extensive research has revealed that a diet consisting of fruits, vegetables, spices, and grains has the potential to prevent cancer (Fig. 8). The specific substances in these dietary foods that are responsible for preventing cancer and the mechanisms by which they achieve this have also been examined extensively. Various phytochemicals have been identified in fruits, vegetables, spices, and grains that exhibit chemopreventive potential (Fig. 9), and numerous studies have shown that a proper diet can help protect against cancer (46, 67�69). Below is a description of selected dietary agents and diet-derived phytochemicals that have been studied extensively to determine their role in cancer prevention.

Fruits & Vegetables

The protective role of fruits and vegetables against cancers that occur in various anatomical sites is now well supported (46,69). In 1966, Wattenberg (70) proposed for the first time that the regular consumption of certain constituents in fruits and vegetables might provide protection from cancer. Doll and Peto (21) showed that 75�80% of cancer cases diagnosed in the USA in 1981 might have been prevented by lifestyle changes. According to a 1997 estimate, approximately 30�40% of cancer cases worldwide were preventable by feasible dietary means (http://www.dietandcancerreportorg/?p=ER). Several studies have addressed the cancer chemopreventive effects of the active components derived from fruits and vegetables.

More than 25,000 different phytochemicals have been identified that may have potential against various cancers. These phytochemicals have advantages because they are safe and usually target multiple cell-signaling pathways (71). Major chemopreventive compounds identified from fruits and vegetables includes carotenoids, vitamins, resveratrol, quercetin, silymarin, sulphoraphane and indole-3-carbinol.

Carotenoids

Various natural carotenoids present in fruits and vegetables were reported to have anti-inflammatory and anticarcinogenic activity. Lycopene is one of the main carotenoids in the regional Mediterranean diet and can account for 50% of the carotenoids in human serum. Lycopene is present in fruits, including watermelon, apricots, pink guava, grapefruit, rosehip, and tomatoes. A wide variety of processed tomato- based products account for more than 85% of dietary lycopene. The anticancer activity of lycopene has been demonstrated in both in vitro and in vivo tumor models as well as in humans. The proposed mechanisms for the anticancer effect of lycopene involve ROS scavenging, up- regulation of detoxification systems, interference with cell proliferation, induction of gap-junctional communication, inhibition of cell-cycle progression, and modulation of signal transduction pathways. Other carotenoids reported to have anticancer activity include beta-carotene, alpha-carotene, lutein, zeaxanthin, beta-cryptoxanthin, fucoxanthin, astaxanthin, capsanthin, crocetin, and phytoene (72).

Resveratrol

The stilbene resveratrol has been found in fruits such as grapes, peanuts, and berries. Resveratrol exhibits anticancer properties against a wide variety of tumors, including lymphoid and myeloid cancers, multiple myeloma, and cancers of the breast, prostate, stomach, colon, and pancreas. The growth-inhibitory effects of resveratrol are mediated through cell-cycle arrest; induction of apoptosis via Fas/ CD95, p53, ceramide activation, tubulin polymerization, mitochondrial and adenylyl cyclase pathways; up-regulation of p21 p53 and Bax; down-regulation of survivin, cyclin D1, cyclin E, Bcl-2, Bcl-xL, and cellular inhibitor of apoptosis proteins; activation of caspases; suppression of nitric oxide synthase; suppression of transcription factors such as NF-?B, AP-1, and early growth response-1; inhibition of cyclooxyge- nase-2 (COX-2) and lipoxygenase; suppression of adhesion molecules; and inhibition of angiogenesis, invasion, and metastasis. Limited data in humans have revealed that resver- atrol is pharmacologically safe. As a nutraceutical, resveratrol is commercially available in the USA and Europe in 50 ?g to 60 mg doses. Currently, structural analogues of resveratrol with improved bioavailability are being pursued as potential chemo- preventive and therapeutic agents for cancer (73).

Quercetin

The flavone quercetin (3,3?,4?,5,7-pentahydroxyflavone), one of the major dietary flavonoids, is found in a broad range of fruits, vegetables, and beverages such as tea and wine, with a daily intake in Western countries of 25�30 mg. The antioxidant, anti-inflammatory, antiproliferative, and apoptotic effects of the molecule have been largely analyzed in cell culture models, and it is known to block NF-?B activation. In animal models, quercetin has been shown to inhibit inflammation and prevent colon and lung cancer. A phase 1 clinical trial indicated that the molecule can be safely administered and that its plasma levels are sufficient to inhibit lymphocyte tyrosine kinase activity. Consumption of quercetin in onions and apples was found to be inversely associated with lung cancer risk in Hawaii. The effect of onions was particularly strong against squamous cell carcinoma. In another study, an increased plasma level of quercetin after a meal of onions was accompanied by increased resistance to strand breakage in lymphocytic DNA and decreased levels of some oxidative metabolites in the urine (74).

Silymarin

The flavonoid silymarin (silybin, isosilybin, silychristin, silydianin, and taxifolin) is commonly found in the dried fruit of the milk thistle plant Silybum marianum. Although silymarin�s role as an antioxidant and hepatoprotective agent is well known, its role as an anticancer agent is just emerging. The anti-inflammatory effects of silymarin are mediated through suppression of NF-?B-regulated gene products, in- cluding COX-2, lipoxygenase (LOX), inducible NO synthase, TNF, and IL-1. Numerous studies have indicated that silymarin is a chemopreventive agent in vivo against various carcinogens/tumor promoters, including UV light, 7,12-dime- thylbenz(a)anthracene (DMBA), phorbol 12-myristate 13-acetate, and others. Silymarin has also been shown to sensitize tumors to chemotherapeutic agents through down- regulation of the MDR protein and other mechanisms. It binds to both estrogen and androgen receptors and down- regulates prostate specific antigen. In addition to its chemo- preventive effects, silymarin exhibits activity against tumors (e.g., prostate and ovary) in rodents. Various clinical trials have indicated that silymarin is bioavailable and pharmaco- logically safe. Studies are now in progress to demonstrate the clinical efficacy of silymarin against various cancers (75).

Indole-3-Carbinol

The flavonoid indole-3-carbinol (I3C) is present in vegetables such as cabbage, broccoli, brussels sprout, cauli- flower, and daikon artichoke. The hydrolysis product of I3C metabolizes to a variety of products, including the dimer 3,3?- diindolylmethane. Both I3C and 3,3?-diindolylmethane exert a variety of biological and biochemical effects, most of which appear to occur because I3C modulates several nuclear transcription factors. I3C induces phase 1 and phase 2 enzymes that metabolize carcinogens, including estrogens. I3C has also been found to be effective in treating some cases of recurrent respiratory papillomatosis and may have other clinical uses (76).

Sulforaphane

Sulforaphane (SFN) is an isothiothiocyanate found in cruciferous vegetables such as broccoli. Its chemopreventive effects have been established in both in vitro and in vivo studies. The mechanisms of action of SFN include inhibition of phase 1 enzymes, induction of phase 2 enzymes to detoxify carcinogens, cell-cycle arrest, induction of apoptosis, inhibi- tion of histone deacetylase, modulation of the MAPK pathway, inhibition of NF-?B, and production of ROS. Preclinical and clinical studies of this compound have suggested its chemopreventive effects at several stages of carcinogenesis. In a clinical trial, SFN was given to eight healthy women an hour before they underwent elective reduction mammoplasty. Induction in NAD(P)H/quinone oxidoreductase and heme oxygenase-1 was observed in the breast tissue of all patients, indicating the anticancer effect of SFN (77).

Teas & Spices

Spices are used all over the world to add flavor, taste, and nutritional value to food. A growing body of research has demonstrated that phytochemicals such as catechins (green tea), curcumin (turmeric), diallyldisulfide (garlic), thymoquinone (black cumin) capsaicin (red chili), gingerol (ginger), anethole (licorice), diosgenin (fenugreek) and eugenol (clove, cinnamon) possess therapeutic and preventive potential against cancers of various anatomical origins. Other phytochemicals with this potential include ellagic acid (clove), ferulic acid (fennel, mustard, sesame), apigenin (coriander, parsley), betulinic acid (rosemary), kaempferol (clove, fenugreek), sesamin (sesame), piperine (pepper), limonene (rose- mary), and gambogic acid (kokum). Below is a description of some important phytochemicals associated with cancer.

Catechins

More than 3,000 studies have shown that catechins derived from green and black teas have potential against various cancers. A limited amount of data are also available from green tea polyphenol chemoprevention trials. Phase 1 trials of healthy volunteers have defined the basic biodistribution patterns, pharmacokinetic parameters, and preliminary safety profiles for short-term oral administration of various green tea preparations. The consumption of green tea appears to be relatively safe. Among patients with established premalignant conditions, green tea derivatives have shown potential efficacy against cervical, prostate, and hepatic malignancies without inducing major toxic effects. One novel study determined that even persons with solid tumors could safely consume up to 1 g of green tea solids, the equivalent of approximately 900 ml of green tea, three times daily. This observation supports the use of green tea for both cancer prevention and treatment (78).

Curcumin

Curcumin is one of the most extensively studied com- pounds isolated from dietary sources for inhibition of inflammation and cancer chemoprevention, as indicated by almost 3000 published studies. Studies from our laboratory showed that curcumin inhibited NF-?B and NF-?B-regulated gene expression in various cancer cell lines. In vitro and in vivo studies showed that this phytochemical inhibited inflammation and carcinogenesis in animal models, including breast, esophageal, stomach, and colon cancer models. Other studies showed that curcumin inhibited ulcerative proctitis and Crohn�s disease, and one showed that curcumin inhibited ulcerative colitis in humans. Another study evaluated the effect of a combination of curcumin and piperine in patients with tropical pancreatitis. One study conducted in patients with familial adenomatous polyposis showed that curcumin has a potential role in inhibiting this condition. In that study, all five patients were treated with curcumin and quercetin for a mean of 6 months and had a decreased polyp number (60.4%) and size (50.9%) from baseline with minimal adverse effects and no laboratory-determined abnormalities.

The pharmacodynamic and pharmacokinetic effects of oral Curcuma extract in patients with colorectal cancer have also been studied. In a study of patients with advanced colorectal cancer refractory to standard chemotherapies, 15 patients received Curcuma extract daily for up to 4 months. Results showed that oral Curcuma extract was well tolerated, and dose-limiting toxic effects were not observed. Another study showed that in patients with advanced colorectal cancer, a daily dose of 3.6 g of curcumin engendered a 62% decrease in inducible prostaglandin E2 production on day 1 and a 57% decrease on day 29 in blood samples taken 1 h after dose administration.

An early clinical trial with 62 cancer patients with external cancerous lesions at various sites (breast, 37; vulva, 4; oral, 7; skin, 7; and others, 11) reported reductions in the sense of smell (90% of patients), itching (almost all patients), lesion size and pain (10% of patients), and exudates (70% of patients) after topical application of an ointment containing curcumin. In a phase 1 clinical trial, a daily dose of 8,000 mg of curcumin taken by mouth for 3 months resulted in histologic improvement of precancerous lesions in patients with uterine cervical intraepithelial neoplasm (one of four patients), intestinal metaplasia (one of six patients), bladder cancer (one of two patients), and oral leukoplakia (two of seven patients).

Results from another study conducted by our group showed that curcumin inhibited constitutive activation of NF- ?B, COX-2, and STAT3 in peripheral blood mononuclear cells from the 29 multiple myeloma patients enrolled in this study. Curcumin was given in doses of 2, 4, 8, or 12 g/day orally. Treatment with curcumin was well tolerated with no adverse events. Of the 29 patients, 12 underwent treatment for 12 weeks and 5 completed 1 year of treatment with stable disease. Other studies from our group showed that curcumin inhibited pancreatic cancer. Curcumin down-regulated the expression of NF-?B, COX-2, and phosphorylated STAT3 in peripheral blood mononuclear cells from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers). These studies showed that curcumin is a potent anti-inflammatory and chemopreventive agent. A detailed description of curcumin and its anticancer properties can be found in one of our recent reviews (79).

Diallyldisulfide

Diallyldisulfide, isolated from garlic, inhibits the growth and proliferation of a number of cancer cell lines including colon, breast, glioblastoma, melanoma, and neuroblastoma cell lines. Recent studies showed that this compound induces apoptosis in Colo 320 DM human colon cancer cells by inhibiting COX-2, NF-?B, and ERK-2. It has been shown to inhibit a number of cancers including dimethylhydrazine-induced colon cancer, benzo[a]pyrene-induced neoplasia, and glutathione S-transferase activity in mice; benzo[a]pyrene-induced skin carcinogenesis in mice; N-nitrosomethylbenzylamine-induced esophageal cancer in rats; N-nitrosodiethylamine-induced forestomach neoplasia in female A/J mice; aristolochic acid-induced forestomach carcinogenesis in rats; diethylnitrosamine-induced glutathione S-transferase positive foci in rat liver; 2-amino- 3-methylimidazo[4,5-f]quinoline-induced hepatocarcinogen- esis in rats; and diethylnitrosamine-induced liver foci and hepatocellular adenomas in C3H mice. Diallyldisulfide has also been shown to inhibit mutagenesis or tumorigenesis induced by vinyl carbamate and N-nitrosodimethylamine; aflatoxin B1-induced and N-nitrosodiethylamine-induced liver preneoplastic foci in rats; arylamine N-acetyltransfer- ase activity and 2-aminofluorene-DNA adducts in human promyelocytic leukemia cells; DMBA-induced mouse skin tumors; N-nitrosomethylbenzylamine-induced mutation in rat esophagus; and diethylstilbesterol-induced DNA ad- ducts in the breasts of female ACI rats.

Diallyldisulfide is believed to bring about an anticarcino- genic effect through a number of mechanisms, such as scavenging of radicals; increasing gluathione levels; increasing the activities of enzymes such as glutathione S-transferase and catalase; inhibiting cytochrome p4502E1 and DNA repair mechanisms; and preventing chromosomal damage (80).

Thymoquinone

The chemotherapeutic and chemoprotective agents from black cumin include thymoquinone (TQ), dithymoquinone (DTQ), and thymohydroquinone, which are present in the oil of this seed. TQ has antineoplastic activity against various tumor cells. DTQ also contributes to the chemotherapeutic effects of Nigella sativa. In vitro study results indicated that DTQ and TQ are equally cytotoxic to several parental cell lines and to their corresponding multidrug-resistant human tumor cell lines. TQ induces apoptosis by p53-dependent and p53-independent pathways in cancer cell lines. It also induces cell-cycle arrest and modulates the levels of inflammatory mediators. To date, the chemotherapeutic potential of TQ has not been tested, but numerous studies have shown its promising anticancer effects in animal models. TQ suppresses carcinogen-induced forestomach and skin tumor formation in mice and acts as a chemopreventive agent at the early stage of skin tumorigenesis. Moreover, the combination of TQ and clinically used anticancer drugs has been shown to improve the drug�s therapeutic index, prevents nontumor tissues from sustaining chemotherapy-induced damage, and enhances the antitumor activity of drugs such as cisplatin and ifosfamide. A very recent report from our own group established that TQ affects the NF-?B signaling pathway by suppressing NF-?B and NF-?B-regulated gene products (81).

Capsaicin

The phenolic compound capsaicin (t8-methyl-N-vanillyl- 6-nonenamide), a component of red chili, has been extensively studied. Although capsaicin has been suspected to be a carcinogen, a considerable amount of evidence suggests that it has chemopreventive effects. The antioxidant, anti-inflammatory, and antitumor properties of capsaicin have been established in both in vitro and in vivo systems. For example, showed that capsaicin can suppress the TPA-stimulated activation of NF-?B and AP-1 in cultured HL-60 cells. In addition, capsaicin inhibited the constitutive activation of NF-?B in malignant melanoma cells. Furthermore, capsaicin strongly suppressed the TPA-stimulated activation of NF-?B and the epidermal activation of AP-1 in mice. Another proposed mechanism of action of capsaicin is its interaction with xenobiotic metaboliz- ing enzymes, involved in the activation and detoxification of various chemical carcinogens and mutagens. Metabolism of capsaicin by hepatic enzymes produces reactive phenoxy radical intermediates capable of binding to the active sites of enzymes and tissue macromolecules.

Capsaicin can inhibit platelet aggregation and suppress calcium-ionophore�stimulated proinflammatory responses, such as the generation of superoxide anion, phospholipase A2 activity, and membrane lipid peroxidation in macro- phages. It acts as an antioxidant in various organs of laboratory animals. Anti-inflammatory properties of capsaicin against carcinogen-induced inflammation have also been reported in rats and mice. Capsaicin has exerted protective effects against ethanol-induced gastric mucosal injury, hem- orrhagic erosion, lipid peroxidation, and myeloperoxidase activity in rats that was associated with suppression of COX- 2. While lacking intrinsic tumor-promoting activity, capsaicin inhibited TPA-promoted mouse skin papillomagenesis (82).

Gingerol

Gingerol, a phenolic substance mainly present in the spice ginger (Zingiber officinale Roscoe), has diverse pharmacologic effects including antioxidant, antiapoptotic, and anti-inflammatory effects. Gingerol has been shown to have anticancer and chemopreventive properties, and the proposed mechanisms of action include the inhibition of COX-2 expression by blocking of the p38 MAPK�NF-?B signaling pathway. A detailed report on the cancer-preventive ability of gingerol was presented in a recent review by Shukla and Singh (83).

Anethole

Anethole, the principal active component of the spice fennel, has shown anticancer activity. In 1995, Al-Harbi et al. (84) studied the antitumor activity of anethole against Ehrlich ascites carcinoma induced in a tumor model in mice. The study revealed that anethole increased survival time, reduced tumor weight, and reduced the volume and body weight of the EAT-bearing mice. It also produced a significant cytotoxic effect in the EAT cells in the paw, reduced the levels of nucleic acids and MDA, and increased NP-SH concentrations.

The histopathological changes observed after treatment with anethole were comparable to those after treatment with the standard cytotoxic drug cyclophosphamide. The frequency of micronuclei occurrence and the ratio of polychromatic erythrocytes to normochromatic erythrocytes showed anethole to be mitodepressive and nonclastogenic in the femoral cells of mice. In 1996, Sen et al., (85) studied the NF-?B inhibitory activity of a derivative of anethole and anetholdithiolthione. Their study results showed that anethole inhibited H2O2, phorbol myristate acetate or TNF alpha induced NF-?B activation in human jurkat T-cells (86) studied the anticarcino- genic activity of anethole trithione against DMBA induced in a rat mammary cancer model. The study results showed that this phytochemical inhibited mammary tumor growth in a dose- dependent manner.

Nakagawa and Suzuki (87) studied the metabolism and mechanism of action of trans-anethole (anethole) and the estrogenlike activity of the compound and its metabolites in freshly isolated rat hepatocytes and cultured MCF-7 human breast cancer cells. The results suggested that the biotransformation of anethole induces a cytotoxic effect at higher concentrations in rat hepatocytes and an estrogenic effect at lower concentrations in MCF-7 cells on the basis of the concentrations of the hydroxylated intermediate, 4OHPB. Results from preclinical studies have suggested that the organosulfur compound anethole dithiolethione may be an effective chemopreventive agent against lung cancer. Lam et al, (88) conducted a phase 2b trial of anethole dithiolethione in smokers with bronchial dysplasia. The results of this clinical trial suggested that anethole dithiolethione is a potentially efficacious chemopreventive agent against lung cancer.

Diosgenin

Diosgenin, a steroidal saponin present in fenugreek, has been shown to suppress inflammation, inhibit proliferation, and induce apoptosis in various tumor cells. Research during the past decade has shown that diosgenin suppresses prolif- eration and induces apoptosis in a wide variety of cancer cells lines. Antiproliferative effects of diosgenin are mediated through cell-cycle arrest, disruption of Ca2+ homeostasis, activation of p53, release of apoptosis-inducing factor, and modulation of caspase-3 activity. Diosgenin also inhibits azoxymethane-induced aberrant colon crypt foci, has been shown to inhibit intestinal inflammation, and modulates the activity of LOX and COX-2. Diosgenin has also been shown to bind to the chemokine receptor CXCR3, which mediates inflammatory responses. Results from our own laboratory have shown that diosgenin inhibits osteoclastogenesis, cell invasion, and cell proliferation through Akt down-regulation, I?B kinase activation, and NF-?B-regulated gene expression (89).

Eugenol

Eugenol is one of the active components of cloves. Studies conducted by Ghosh et al. (90) showed that eugenol suppressed the proliferation of melanoma cells. In a B16 xenograft study, eugenol treatment produced a significant tumor growth delay, an almost 40% decrease in tumor size, and a 19% increase in the median time to end point. Of more importance, 50% of the animals in the control group died of metastatic growth, whereas none in the eugenol treatment group showed any signs of cell invasion or metastasis. In 1994, Sukumaran et al. (91) showed that eugenol DMBA induced skin tumors in mice. The same study showed that eugenol inhibited superoxide formation and lipid peroxidation and the radical scavenging activity that may be responsible for its chemopreventive action. Studies conducted by Imaida et al. (92) showed that eugenol enhanced the development of 1,2- dimethylhydrazine-induced hyperplasia and papillomas in the forestomach but decreased the incidence of 1-methyl-1-nitro- sourea-induced kidney nephroblastomas in F344 male rats.

Another study conducted by Pisano et al. (93) demonstrated that eugenol and related biphenyl (S)-6,6?-dibromo-dehydrodieugenol elicit specific antiproliferative activity on neuroectodermal tumor cells, partially triggering apoptosis. In 2003, Kim et al. (94) showed that eugenol suppresses COX-2 mRNA expression (one of the main genes implicated in the processes of inflammation and carcinogenesis) in HT-29 cells and lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells. Another study by Deigner et al. (95) showed that 1?-hydroxyeugenol is a good inhibitor of 5-lipoxygenase and Cu(2+)-mediated low-density lipoprotein oxidation. The studies by Rompelberg et al. (96) showed that in vivo treatment of rats with eugenol reduced the mutagenicity of benzopyrene in the Salmonella typhimurium mutagenicity assay, whereas in vitro treatment of cultured cells with eugenol increased the genotoxicity of benzopyrene.

Wholegrain Foods

The major wholegrain foods are wheat, rice, and maize; the minor ones are barley, sorghum, millet, rye, and oats. Grains form the dietary staple for most cultures, but most are eaten as refined-grain products in Westernized countries (97). Whole grains contain chemopreventive antioxidants such as vitamin E, tocotrienols, phenolic acids, lignans, and phytic acid. The antioxidant content of whole grains is less than that of some berries but is greater than that of common fruits or vegetables (98). The refining process concentrates the carbo- hydrate and reduces the amount of other macronutrients, vitamins, and minerals because the outer layers are removed. In fact, all nutrients with potential preventive actions against cancer are reduced. For example, vitamin E is reduced by as much as 92% (99).

Wholegrain intake was found to reduce the risk of several cancers including those of the oral cavity, pharynx, esophagus, gallbladder, larynx, bowel, colorectum, upper digestive tract, breasts, liver, endometrium, ovaries, prostate gland, bladder, kidneys, and thyroid gland, as well as lymphomas, leukemias, and myeloma (100,101). Intake of wholegrain foods in these studies reduced the risk of cancers by 30�70% (102).

How do whole grains reduce the risk of cancer? Several potential mechanisms have been described. For instance, insoluble fibers, a major constituent of whole grains, can reduce the risk of bowel cancer (103). Additionally, insoluble fiber undergoes fermentation, thus producing short-chain fatty acids such as butyrate, which is an important suppressor of tumor formation (104). Whole grains also mediate favorable glucose response, which is protective against breast and colon cancers (105). Also, several phytochemicals from grains and pulses were reported to have chemopreventive action against a wide variety of cancers. For example, isoflavones (including daidzein, genistein, and equol) are nonsteroidal diphenolic com- pounds that are found in leguminous plants and have antiproliferative activities. Findings from several, but not all, studies have shown significant correlations between an isoflavone-rich soy-based diet and reduced incidence of cancer or mortality from cancer in humans. Our laboratory has shown that tocotrienols, but not tocopherols, can suppress NF-?B activation induced by most carcinogens, thus leading to suppression of various genes linked with proliferation, survival, invasion, and angiogenesis of tumors (106).

Observational studies have suggested that a diet rich in soy isoflavones (such as the typical Asian diet) is one of the most significant contributing factors for the lower observed incidence and mortality of prostate cancers in Asia. On the basis of findings about diet and of urinary excretion levels associated with daidzein, genistein, and equol in Japanese subjects compared with findings in American or European subjects, the isoflavonoids in soy products were proposed to be the agents responsible for reduced cancer risk. In addition to its effect on breast cancer, genistein and related isoflavones also inhibit cell growth or the development of chemically induced cancers in the stomach, bladder, lung, prostate, and blood (107).

Vitamins

Although controversial, the role of vitamins in cancer chemoprevention is being evaluated increasingly. Fruits and vegetables are the primary dietary sources of vitamins except for vitamin D. Vitamins, especially vitamins C, D, and E, are reported to have cancer chemopreventive activity without apparent toxicity.

Epidemiologic study findings suggest that the anticancer/ chemopreventive effects of vitamin C against various types of cancers correlate with its antioxidant activities and with the inhibition of inflammation and gap junction intercellular communication. Findings from a recent epidemiologic study showed that a high vitamin C concentration in plasma had an inverse relationship with cancer-related mortality. In 1997, expert panels at the World Cancer Research Fund and the American Institute for Cancer Research estimated that vitamin C can reduce the risk of cancers of the stomach, mouth, pharynx, esophagus, lung, pancreas, and cervix (108).

The protective effects of vitamin D result from its role as a nuclear transcription factor that regulates cell growth, differentiation, apoptosis, and a wide range of cellular mechanisms central to the development of cancer (109).

Exercise/Physical Activity

There is extensive evidence suggesting that regular physical exercise may reduce the incidence of various cancers. A sedentary lifestyle has been associated with most chronic illnesses. Physical inactivity has been linked with increased risk of cancer of the breast, colon, prostate, and pancreas and of melanoma (110). The increased risk of breast cancer among sedentary women that has been shown to be due to lack of exercise has been associated with a higher serum concentration of estradiol, lower concentration of hormone- binding globulin, larger fat masses, and higher serum insulin levels. Physical inactivity can also increase the risk of colon cancer (most likely because of an increase in GI transit time, thereby increasing the duration of contact with potential carcinogens), increase the circulating levels of insulin (pro- mote proliferation of colonic epithelial cells), alter prosta- glandin levels, depress the immune function, and modify bile acid metabolism. Additionally, men with a low level of physical activity and women with a larger body mass index were more likely to have a Ki-ras mutation in their tumors, which occurs in 30�50% of colon cancers. A reduction of almost 50% in the incidence of colon cancer was observed among those with the highest levels of physical activity (111). Similarly, higher blood testosterone and IGF-1 levels and suppressed immunity due to lack of exercise may increase the incidence of prostate cancer. One study indicated that sedentary men had a 56% and women a 72% higher incidence of melanoma than did those exercising 5�7 days per week (112).

Caloric Restrictions

Fasting is a type of caloric restriction (CR) that is prescribed in most cultures. Perhaps one of the first reports that CR can influence cancer incidence was published in 1940 on the formation of skin tumors and hepatoma in mice (113, 114). Since then, several reports on this subject have been published (115, 116). Dietary restriction, especially CR, is a major modifier in experimental carcinogenesis and is known to significantly decrease the incidence of neoplasms. Gross and Dreyfuss reported that a 36% restriction in caloric intake dramatically decreased radiation-induced solid tumors and/or leukemias (117, 118). Yoshida et al. (119) also showed that CR reduces the incidence of myeloid leukemia induced by a single treatment with whole-body irradiation in mice.

How CR reduces the incidence of cancer is not fully understood. CR in rodents decreases the levels of plasma glucose and IGF-1 and postpones or attenuates cancer and inflammation without irreversible adverse effects (120). Most of the studies done on the effect of CR in rodents are long- term; however, that is not possible in humans, who routinely practice transient CR. The effect that transient CR has on cancer in humans is unclear.

Conclusions

On the basis of the studies described above, we propose a unifying hypothesis that all lifestyle factors that cause cancer (carcinogenic agents) and all agents that prevent cancer (chemopreventive agents) are linked through chronic inflammation (Fig. 10). The fact that chronic inflammation is closely linked to the tumorigenic pathway is evident from numerous lines of evidence.

First, inflammatory markers such as cytokines (such as TNF, IL-1, IL-6, and chemokines), enzymes (such as COX-2, 5-LOX, and matrix metalloproteinase-9 [MMP-9]), and adhesion molecules (such as intercellular adhesion molecule 1, endothelium leukocyte adhesion molecule 1, and vascular cell adhesion molecule 1) have been closely linked with tumorigenesis. Second, all of these inflammatory gene products have been shown to be regulated by the nuclear transcription factor, NF-?B. Third, NF-?B has been shown to control the expression of other gene products linked with tumorigenesis such as tumor cell survival or antiapoptosis (Bcl-2, Bcl-xL, IAP-1, IAP-2, XIAP, survivin, cFLIP, and TRAF-1), proliferation (such as c-myc and cyclin D1), invasion (MMP-9), and angiogenesis (vascular endothelial growth factor). Fourth, in most cancers, chronic inflammation precedes tumorigenesis.

Fifth, most carcinogens and other risk factors for cancer, including cigarette smoke, obesity, alcohol, hyperglycemia, infectious agents, sunlight, stress, food carcinogens, and environmental pollutants, have been shown to activate NF- ?B. Sixth, constitutive NF-?B activation has been encountered in most types of cancers. Seventh, most chemotherapeutic agents and ?-radiation, used for the treatment of cancers, lead to activation of NF-?B. Eighth, activation of NF-?B has been linked with chemoresistance and radioresistance. Ninth, sup- pression of NF-?B inhibits the proliferation of tumors, leads to apoptosis, inhibits invasion, and suppresses angiogenesis. Tenth, polymorphisms of TNF, IL-1, IL-6, and cyclin D1 genes encountered in various cancers are all regulated by NF-?B. Also, mutations in genes encoding for inhibitors of NF-?B have been found in certain cancers. Eleventh, almost all chemopreventive agents described above have been shown to suppress NF-?B activation. In summary, this review outlines the preventability of cancer based on the major risk factors for cancer. The percentage of cancer-related deaths attributable to diet and tobacco is as high as 60�70% worldwide.

ACKNOWLEDGEMENT

This research was supported by The Clayton Foundation for Research (to B.B.A.).

References:

1. L. N. Kolonel, D. Altshuler, and B. E. Henderson. The
multiethnic cohort study: exploring genes, lifestyle and cancer
risk. Nat. Rev. Cancer. 4:519�27 (2004) doi:10.1038/nrc1389.
2. J. K. Wiencke. Impact of race/ethnicity on molecular pathways
in human cancer. Nat. Rev. Cancer. 4:79�84 (2004) doi:10.1038/
nrc1257.
3. R. G. Ziegler, R. N. Hoover, M. C. Pike, A. Hildesheim, A. M.
Nomura, D. W. West, A. H. Wu-Williams, L. N. Kolonel, P. L.
Horn-Ross, J. F. Rosenthal, and M. B. Hyer. Migration patterns
and breast cancer risk in Asian-American women. J. Natl.
Cancer Inst. 85:1819�27 (1993) doi:10.1093/jnci/85.22.1819.
4. W. Haenszel and M. Kurihara. Studies of Japanese migrants. I.
Mortality from cancer and other diseases among Japanese in
the United States. J. Natl. Cancer Inst. 40:43�68 (1968).
5. A. S. Hamilton and T. M. Mack. Puberty and genetic
susceptibility to breast cancer in a case-control study in twins.
N. Engl. J. Med. 348:2313�22 (2003) doi:10.1056/NEJ
Moa021293.
6. A. Jemal, R. Siegel, E. Ward, T. Murray, J. Xu, and M. J. Thun.
Cancer statistics, 2007. CA Cancer J. Clin. 57:43�66 (2007).
7. F. Brayand, and B. Moller. Predicting the future burden of
cancer. Nat. Rev. Cancer. 6:63�74 (2006) doi:10.1038/nrc1781.
8. P. Lichtenstein, N. V. Holm, P. K. Verkasalo, A. Iliadou, J.
Kaprio, M. Koskenvuo, E. Pukkala, A. Skytthe, and K.
Hemminki. Environmental and heritable factors in the causation
of cancer�analyses of cohorts of twins from Sweden,
Denmark, and Finland. N. Engl. J. Med. 343:78�85 (2000)
doi:10.1056/NEJM200007133430201.
9. K. R. Loeb, and L. A. Loeb. Significance of multiple mutations
in cancer. Carcinogenesis. 21:379�85 (2000) doi:10.1093/carcin/
21.3.379.
10. W. C. Hahn, and R. A. Weinberg. Modelling the molecular
circuitry of cancer. Nat. Rev. Cancer. 2:331�41 (2002) doi:
10.1038/nrc795.
11. L. A. Mucci, S. Wedren, R. M. Tamimi, D. Trichopoulos, and H.
O. Adami. The role of gene-environment interaction in the
aetiology of human cancer: examples from cancers of the large
bowel, lung and breast. J. Intern. Med. 249:477�93 (2001)
doi:10.1046/j.1365-2796.2001.00839.x.
12. K. Czene, and K. Hemminki. Kidney cancer in the Swedish
Family Cancer Database: familial risks and second primary
malignancies. Kidney Int. 61:1806�13 (2002) doi:10.1046/j.1523-
1755.2002.00304.x.
13. P. Irigaray, J. A. Newby, R. Clapp, L. Hardell, V. Howard, L.
Montagnier, S. Epstein, and D. Belpomme. Lifestyle-related
factors and environmental agents causing cancer: an overview.
Biomed. Pharmacother. 61:640�58 (2007) doi:10.1016/j.bio
pha.2007.10.006.
14. M. F. Denissenko, A. Pao, M. Tang, and G. P. Pfeifer.
Preferential formation of benzo[a]pyrene adducts at lung
cancer mutational hotspots in P53. Science. 274:430�2 (1996)
doi:10.1126/science.274.5286.430.
15. R. J. Anto, A. Mukhopadhyay, S. Shishodia, C. G. Gairola, and
B. B. Aggarwal. Cigarette smoke condensate activates nuclear
transcription factor-kappaB through phosphorylation and degradation
of IkappaB(alpha): correlation with induction of
cyclooxygenase-2. Carcinogenesis. 23:1511�8 (2002) doi:
10.1093/carcin/23.9.1511.
16. S. Shishodiaand, and B. B. Aggarwal. Cyclooxygenase (COX)-2
inhibitor celecoxib abrogates activation of cigarette smokeinduced
nuclear factor (NF)-kappaB by suppressing activation
of IkappaBalpha kinase in human non-small cell lung carcinoma:
correlation with suppression of cyclin D1, COX-2, and
matrix metalloproteinase-9. Cancer Res. 64:5004�12 (2004)
doi:10.1158/0008-5472.CAN-04-0206.
17. H. Ichikawa, Y. Nakamura, Y. Kashiwada, and B. B. Aggarwal.
Anticancer drugs designed by mother nature: ancient drugs but
modern targets. Curr Pharm Des. 13:3400�16 (2007)
doi:10.2174/138161207782360500.
18. A. J. Tuyns. Epidemiology of alcohol and cancer. Cancer Res.
39:2840�3 (1979).
19. H. Maier, E. Sennewald, G. F. Heller, and H. Weidauer.
Chronic alcohol consumption�the key risk factor for pharyngeal
cancer. Otolaryngol. Head Neck Surg. 110:168�73 (1994).
20. H. K. Seitz, F. Stickel, and N. Homann. Pathogenetic mechanisms
of upper aerodigestive tract cancer in alcoholics. Int. J.
Cancer. 108:483�7 (2004) doi:10.1002/ijc.11600.
21. R. Doll, and R. Peto. The causes of cancer: quantitative
estimates of avoidable risks of cancer in the United States
today. J. Natl. Cancer Inst. 66:1191�308 (1981).
22. R. R. Williams, and J. W. Horm. Association of cancer sites
with tobacco and alcohol consumption and socioeconomic
status of patients: interview study from the Third National
Cancer Survey. J. Natl. Cancer Inst. 58:525�47 (1977).
23. N. Hamajima et al. Alcohol, tobacco and breast cancer�
collaborative reanalysis of individual data from 53 epidemiological
studies, including 58,515 women with breast cancer and
95,067 women without the disease. Br. J. Cancer. 87:1234�45
(2002) doi:10.1038/sj.bjc.6600596.
24. M. P. Longnecker, P. A. Newcomb, R. Mittendorf, E. R.
Greenberg, R. W. Clapp, G. F. Bogdan, J. Baron, B. MacMahon,
and W. C. Willett. Risk of breast cancer in relation to lifetime
alcohol consumption. J. Natl. Cancer Inst. 87:923�9 (1995)
doi:10.1093/jnci/87.12.923.
25. F. Stickel, D. Schuppan, E. G. Hahn, and H. K. Seitz.
Cocarcinogenic effects of alcohol in hepatocarcinogenesis.
Gut. 51:132�9 (2002) doi:10.1136/gut.51.1.132.
26. H. K. Seitz, G. Poschl, and U. A. Simanowski. Alcohol and
cancer. Recent Dev Alcohol. 14:67�95 (1998) doi:10.1007/0-306-
47148-5_4.
27. H. K. Seitz, S. Matsuzaki, A. Yokoyama, N. Homann, S.
Vakevainen, and X. D. Wang. Alcohol and cancer. Alcohol
Clin. Exp. Res. 25:137S�143S (2001).
28. F. Donato, U. Gelatti, R. M. Limina, and G. Fattovich.
Southern Europe as an example of interaction between various
environmental factors: a systematic review of the epidemiologicevidence. Oncogene. 25:3756�70 (2006) doi:10.1038/sj. onc.1209557.29. G. Poschl, and H. K. Seitz. Alcohol and cancer. Alcohol
Alcohol. 39:155�65 (2004) doi:10.1093/alcalc/agh057.
30. G. Szabo, P. Mandrekar, S. Oak, and J. Mayerle. Effect of
ethanol on inflammatory responses. Implications for pancreatitis.
Pancreatology. 7:115�23 (2007) doi:10.1159/000104236.
31. B. B. Aggarwal. Nuclear factor-kappaB: the enemy within.
Cancer Cell. 6:203�208 (2004) doi:10.1016/j.ccr.2004.09.003.
32. M. Kuratsune, S. Kohchi, and A. Horie. Carcinogenesis in the
esophagus. I. Penetration of benzo(a) pyrene and other hydrocarbons
into the esophageal mucosa. Gann. 56:177�87 (1965).
33. C. La Vecchia, A. Tavani, S. Franceschi, F. Levi, G. Corrao,
and E. Negri. Epidemiology and prevention of oral cancer. Oral
Oncol. 33:302�312 (1997).
34. P. Boffetta, M. Hashibe, C. La Vecchia, W. Zatonski, and J.
Rehm. The burden of cancer attributable to alcohol drinking.
Int. J. Cancer. 119:884�887 (2006) doi:10.1002/ijc.21903.
35. W. C. Willett. Diet and cancer. Oncologist. 5:393�404 (2000)
doi:10.1634/theoncologist.5-5-393.
36. S. A. Bingham, R. Hughes, and A. J. Cross. Effect of white
versus red meat on endogenous N-nitrosation in the human
colon and further evidence of a dose response. J. Nutr.
132:3522S�3525S (2002).
37. A. Chao, M. J. Thun, C. J. Connell, M. L. McCullough, E. J.
Jacobs, W. D. Flanders, C. Rodriguez, R. Sinha, and E. E.
Calle. Meat consumption and risk of colorectal cancer. JAMA.
293:172�182 (2005) doi:10.1001/jama.293.2.172.
38. N. Hogg. Red meat and colon cancer: heme proteins and nitrite
in the gut. A commentary on diet-induced endogenous formation
of nitroso compounds in the GI tract. Free Radic. Biol. Med.
43:1037�1039 (2007) doi:10.1016/j.freeradbiomed.2007.07.006.
39. C. Rodriguez, M. L. McCullough, A. M. Mondul, E. J. Jacobs,
A. Chao, A. V. Patel, M. J. Thun, and E. E. Calle. Meat
consumption among Black and White men and risk of prostate
cancer in the Cancer Prevention Study II Nutrition Cohort.
Cancer Epidemiol. Biomarkers Prev. 15:211�216 (2006)
doi:10.1158/1055-9965.EPI-05-0614.
40. R. Garcia-Closas, M. Garcia-Closas, M. Kogevinas, N. Malats,
D. Silverman, C. Serra, A. Tardon, A. Carrato, G. CastanoVinyals,
M. Dosemeci, L. Moore, N. Rothman, and R. Sinha.
Food, nutrient and heterocyclic amine intake and the risk of
bladder cancer. Eur. J. Cancer. 43:1731�1740 (2007) doi:10.1016/
j.ejca.2007.05.007.
41. A. Tappel. Heme of consumed red meat can act as a catalyst of
oxidative damage and could initiate colon, breast and prostate
cancers, heart disease and other diseases. Med. Hypotheses.
68:562�4 (2007) doi:10.1016/j.mehy.2006.08.025.
42. L. H. O’Hanlon. High meat consumption linked to gastriccancer
risk. Lancet Oncol. 7:287 (2006) doi:10.1016/S1470-2045
(06)70638-6.
43. T. N. Toporcov, J. L. Antunes, and M. R. Tavares. Fat food
habitual intake and risk of oral cancer. Oral Oncol. 40:925�931
(2004) doi:10.1016/j.oraloncology.2004.04.007.
44. O. Dosil-Diaz, A. Ruano-Ravina, J. J. Gestal-Otero, and J. M.
Barros-Dios. Meat and fish consumption and risk of lung
cancer: A case-control study in Galicia, Spain. Cancer Lett.
252:115�122 (2007) doi:10.1016/j.canlet.2006.12.008.
45. S. N. Lauber, and N. J. Gooderham. The cooked meat derived
genotoxic carcinogen 2-amino-3-methylimidazo[4,5-b]pyridine
has potent hormone-like activity: mechanistic support for a role
in breast cancer. Cancer Res. 67:9597�0602 (2007) doi:10.1158/
0008�5472.CAN-07-1661.
46. D. Divisi, S. Di Tommaso, S. Salvemini, M. Garramone, and R.
Crisci. Diet and cancer. Acta Biomed. 77:118�123 (2006).
47. Y. F. Sasaki, S. Kawaguchi, A. Kamaya, M. Ohshita, K.
Kabasawa, K. Iwama, K. Taniguchi, and S. Tsuda. The comet
assay with 8 mouse organs: results with 39 currently used food
additives. Mutat. Res. 519:103�119 (2002).
48. M. Durando, L. Kass, J. Piva, C. Sonnenschein, A. M. Soto, E.
H. Luque, and M. Munoz-de-Toro. Prenatal bisphenol A
exposure induces preneoplastic lesions in the mammary gland
in Wistar rats. Environ. Health Perspect. 115:80�6 (2007).
49. S. M. Ho, W. Y. Tang, J. Belmonte de Frausto, and G. S.
Prins. Developmental exposure to estradiol and bisphenol A
increases susceptibility to prostate carcinogenesis and epigenetically
regulates phosphodiesterase type 4 variant 4.
Cancer Res. 66:5624�32 (2006) doi:10.1158/0008-5472.CAN-06-
0516.
50. A. Szymanska-Chabowska, J. Antonowicz-Juchniewicz, and R.
Andrzejak. Some aspects of arsenic toxicity and carcinogenicity
in living organism with special regard to its influence on
cardiovascular system, blood and bone marrow. Int. J. Occup.
Med. Environ. Health. 15:101�116 (2002).
51. E. E. Calle, C. Rodriguez, K. Walker-Thurmond, and M. J.
Thun. Overweight, obesity, and mortality from cancer in a
prospectively studied cohort of U.S. adults. N Engl J Med.
348:1625�1638 (2003) doi:10.1056/NEJMoa021423.
52. A. Drewnowski, and B. M. Popkin. The nutrition transition:
new trends in the global diet. Nutr. Rev. 55:31�43 (1997).
53. S. D. Hursting, L. M. Lashinger, L. H. Colbert, C. J. Rogers, K. W.
Wheatley, N. P. Nunez, S. Mahabir, J. C. Barrett, M. R. Forman,
and S. N. Perkins. Energy balance and carcinogenesis: underlying
pathways and targets for intervention. Curr. Cancer Drug Targets.
7:484�491 (2007) doi:10.2174/156800907781386623.
54. A. Nareika, Y. B. Im, B. A. Game, E. H. Slate, J. J. Sanders,
S. D. London, M. F. Lopes-Virella, and Y. Huang. High glucose
enhances lipopolysaccharide-stimulated CD14 expression in
U937 mononuclear cells by increasing nuclear factor kappaB
and AP-1 activities. J. Endocrinol. 196:45�55 (2008) doi:10.
1677/JOE-07-0145.
55. C. H. Tang, Y. C. Chiu, T. W. Tan, R. S. Yang, and W. M. Fu.
Adiponectin enhances IL-6 production in human synovial
fibroblast via an AdipoR1 receptor, AMPK, p38, and NFkappa
B pathway. J. Immunol. 179:5483�5492 (2007).
56. P. Pisani, D. M. Parkin, N. Munoz, and J. Ferlay. Cancer and
infection: estimates of the attributable fraction in 1990. Cancer
Epidemiol. Biomarkers Prev. 6:387�400 (1997).
57. D. M. Parkin. The global health burden of infection-associated
cancers in the year 2002. Int. J. Cancer. 118:3030�3044 (2006)
doi:10.1002/ijc.21731.
58. S. Song, H. C. Pitot, and P. F. Lambert. The human
papillomavirus type 16 E6 gene alone is sufficient to induce
carcinomas in transgenic animals. J. Virol. 73:5887�5893 (1999).
59. B. S. Blumberg, B. Larouze, W. T. London, B. Werner, J. E.
Hesser, I. Millman, G. Saimot, and M. Payet. The relation of
infection with the hepatitis B agent to primary hepatic carcinoma.
Am. J. Pathol. 81:669�682 (1975).
60. T. M. Hagen, S. Huang, J. Curnutte, P. Fowler, V. Martinez, C.
M. Wehr, B. N. Ames, and F. V. Chisari. Extensive oxidative
DNA damage in hepatocytes of transgenic mice with chronic
active hepatitis destined to develop hepatocellular carcinoma.
Proc. Natl. Acad. Sci. U S A. 91:12808�12812 (1994)
doi:10.1073/pnas.91.26.12808.
61. A. L. Jackson, and L. A. Loeb. The contribution of
endogenous sources of DNA damage to the multiple mutations
in cancer. Mutat. Res. 477:7�21 (2001) doi:10.1016/S0027-
5107(01)00091-4.
62. N. De Maria, A. Colantoni, S. Fagiuoli, G. J. Liu, B. K. Rogers,
F. Farinati, D. H. Van Thiel, and R. A. Floyd. Association
between reactive oxygen species and disease activity in chronic
hepatitis C. Free Radic. Biol. Med. 21:291�5 (1996) doi:10.1016/
0891�5849(96)00044-5.
63. K. Koike, T. Tsutsumi, H. Fujie, Y. Shintani, and M. Kyoji.
Molecular mechanism of viral hepatocarcinogenesis. Oncology.
62(Suppl 1):29�37 (2002) doi:10.1159/000048273.
64. D. Belpomme, P. Irigaray, L. Hardell, R. Clapp, L. Montagnier,
S. Epstein, and A. J. Sasco. The multitude and diversity of
environmental carcinogens. Environ. Res. 105:414�429 (2007)
doi:10.1016/j.envres.2007.07.002.
65. Y. S. Guan, Q. He, M. Q. Wang, and P. Li. Nuclear factor kappa
B and hepatitis viruses. Expert Opin. Ther. Targets. 12:265�280
(2008) doi:10.1517/14728222.12.3.265.
66. S. Takayama, H. Takahashi, Y. Matsuo, Y. Okada, and T.
Manabe. Effects of Helicobacter pylori infection on human
pancreatic cancer cell line. Hepatogastroenterology. 54:2387�
2391 (2007).
67. K. A. Steinmetz, and J. D. Potter. Vegetables, fruit, and cancer
prevention: a review. J. Am. Diet Assoc. 96:1027�1039 (1996)
doi:10.1016/S0002�8223(96)00273-8.68. P. Greenwald. Lifestyle and medical approaches to cancer
prevention. Recent Results Cancer Res. 166:1�15 (2005).
69. H. Vainio, and E. Weiderpass. Fruit and vegetables in cancer
prevention. Nutr. Cancer. 54:111�42 (2006) doi:10.1207/
s15327914nc5401_13.
70. L. W. Wattenberg. Chemoprophylaxis of carcinogenesis: a
review. Cancer Res. 26:1520�1526 (1966).
71. B. B. Aggarwal, and S. Shishodia. Molecular targets of dietary
agents for prevention and therapy of cancer. Biochem. Pharmacol.
71:1397�1421 (2006) doi:10.1016/j.bcp.2006.02.009.
72. H. Nishino, M. Murakosh, T. Ii, M. Takemura, M. Kuchide, M.
Kanazawa, X. Y. Mou, S. Wada, M. Masuda, Y. Ohsaka, S.
Yogosawa, Y. Satomi, and K. Jinno. Carotenoids in cancer
chemoprevention. Cancer Metastasis Rev. 21:257�264 (2002)
doi:10.1023/A:1021206826750.
73. K. B. Harikumar, and B. B. Aggarwal. Resveratrol: A multitargeted
agent for age-associated chronic diseases. Cell Cycle.
7:1020�1037 (2008).
74. G. L. Russo. Ins and outs of dietary phytochemicals in cancer
chemoprevention. Biochem. Pharmacol. 74:533�544 (2007)
doi:10.1016/j.bcp.2007.02.014.
75. R. Agarwal, C. Agarwal, H. Ichikawa, R. P. Singh, and B. B.
Aggarwal. Anticancer potential of silymarin: from bench to bed
side. Anticancer Res. 26:4457�98 (2006).
76. E. G. Rogan. The natural chemopreventive compound indole3-carbinol:
state of the science. In Vivo. 20:221�228 (2006).
77. N. Juge, R. F. Mithen, and M. Traka. Molecular basis for
chemoprevention by sulforaphane: a comprehensive review.
Cell Mol Life Sci. 64:1105�27 (2007) doi:10.1007/s00018-007-
6484-5.
78. L. Chen, and H. Y. Zhang. Cancer preventive mechanisms of
the green tea polyphenol (?)-epigallocatechin-3-gallate. Molecules.
12:946�957 (2007).
79. P. Anand, C. Sundaram, S. Jhurani, A. B. Kunnumakkara, and
B. B. Aggarwal. Curcumin and cancer: An “old-age” disease
with an “age-old” solution. Cancer Lett. in press (2008).
80. F. Khanum, K. R. Anilakumar, and K. R. Viswanathan.
Anticarcinogenic properties of garlic: a review. Crit. Rev. Food
Sci. Nutr. 44:479�488 (2004) doi:10.1080/10408690490886700.
81. G. Sethi, K. S. Ahn and B. B. Aggarwal. Targeting NF-kB
activation pathway by thymoquinone: Role in suppression of
antiapoptotic gene products and enhancement of apoptosis. Mole
Cancer Res. in press (2008).
82. Y. J. Surh. Anti-tumor promoting potential of selected spice
ingredients with antioxidative and anti-inflammatory activities:
a short review. Food Chem. Toxicol. 40:1091�1097 (2002)
doi:10.1016/S0278-6915(02)00037-6.
83. Y. Shukla, and M. Singh. Cancer preventive properties of
ginger: a brief review. Food Chem. Toxicol. 45:683�690 (2007)
doi:10.1016/j.fct.2006.11.002.
84. M. M. al-Harbi, S. Qureshi, M. Raza, M. M. Ahmed, A. B.
Giangreco, and A. H. Shah. Influence of anethole treatment on
the tumour induced by Ehrlich ascites carcinoma cells in paw of
Swiss albino mice. Eur. J. Cancer Prev. 4:307�318 (1995)
doi:10.1097/00008469-199508000-00006.
85. C. K. Sen, K. E. Traber, and L. Packer. Inhibition of NF-kappa
B activation in human T-cell lines by anetholdithiolthione.
Biochem. Biophys. Res. Commun. 218:148�53 (1996)
doi:10.1006/bbrc.1996.0026.
86. R. A. Lubet, V. E. Steele, I. Eto, M. M. Juliana, G. J. Kelloff, and
C. J. Grubbs. Chemopreventive efficacy of anethole trithione, Nacetyl-L-cysteine,
miconazole and phenethylisothiocyanate in the
DMBA-induced rat mammary cancer model. Int. J. Cancer.
72:95�101 (1997) doi:10.1002/(SICI)1097-0215(19970703)
72:1<95::AID-IJC14>3.0.CO;2-9.
87. Y. Nakagawa, and T. Suzuki. Cytotoxic and xenoestrogenic
effects via biotransformation of trans-anethole on isolated rat
hepatocytes and cultured MCF-7 human breast cancer cells.
Biochem. Pharmacol. 66:63�73 (2003) doi:10.1016/S0006-2952
(03)00208-9.
88. S. Lam, C. MacAulay, J. C. Le Riche, Y. Dyachkova, A.
Coldman, M. Guillaud, E. Hawk, M. O. Christen, and A. F.
Gazdar. A randomized phase IIb trial of anethole dithiolethione
in smokers with bronchial dysplasia. J. Natl. Cancer Inst.
94:1001�1009 (2002).
89. S. Shishodia, and B. B. Aggarwal. Diosgenin inhibits osteoclastogenesis,
invasion, and proliferation through the downregulation
of Akt, I kappa B kinase activation and NF-kappa B-regulated
gene expression. Oncogene. 25:1463�1473 (2006) doi:10.1038/sj.
onc.1209194.
90. R. Ghosh, N. Nadiminty, J. E. Fitzpatrick, W. L. Alworth, T. J.
Slaga, and A. P. Kumar. Eugenol causes melanoma growth
suppression through inhibition of E2F1 transcriptional activity.
J. Biol. Chem. 280:5812�5819 (2005) doi:10.1074/jbc.
M411429200.
91. K. Sukumaran, M. C. Unnikrishnan, and R. Kuttan. Inhibition
of tumour promotion in mice by eugenol. Indian J. Physiol.
Pharmacol. 38:306�308 (1994).
92. K. Imaida, M. Hirose, S. Yamaguchi, S. Takahashi, and N. Ito.
Effects of naturally occurring antioxidants on combined 1,2-
dimethylhydrazine- and 1-methyl-1-nitrosourea-initiated carcinogenesis
in F344 male rats. Cancer Lett. 55:53�59 (1990)
doi:10.1016/0304-3835(90)90065-6.
93. M. Pisano, G. Pagnan, M. Loi, M. E. Mura, M. G. Tilocca, G.
Palmieri, D. Fabbri, M. A. Dettori, G. Delogu, M. Ponzoni, and
C. Rozzo. Antiproliferative and pro-apoptotic activity of
eugenol-related biphenyls on malignant melanoma cells. Mol
Cancer. 6:8 (2007) doi:10.1186/1476-4598-6-8.
94. S. S. Kim, O. J. Oh, H. Y. Min, E. J. Park, Y. Kim, H. J. Park, Y.
Nam Han, and S. K. Lee. Eugenol suppresses cyclooxygenase-2
expression in lipopolysaccharide-stimulated mouse macrophage
RAW264.7 cells. Life Sci. 73:337�348 (2003) doi:10.1016/S0024�
3205(03)00288-1.
95. H. P. Deigner, G. Wolf, U. Ohlenmacher, and J. Reichling. 1�-
Hydroxyeugenol- and coniferyl alcohol derivatives as effective
inhibitors of 5-lipoxygenase and Cu(2+)-mediated low density
lipoprotein oxidation. Evidence for a dual mechanism. Arzneimittelforschung.
44:956�961 (1994).
96. C. J. Rompelberg, M. J. Steenwinkel, J. G. van Asten, J. H. van
Delft, R. A. Baan, and H. Verhagen. Effect of eugenol on the
mutagenicity of benzo[a]pyrene and the formation of benzo[a]
pyrene-DNA adducts in the lambda-lacZ-transgenic mouse.
Mutat. Res. 369:87�96 (1996) doi:10.1016/S0165-1218(96)90052-X.
97. D. P. Richardson. The grain, the wholegrain and nothing but
the grain: the science behind wholegrain and the reduced risk of
heart disease and cancer. Nutr. Bull. 25:353�360 (2000)
doi:10.1046/j.1467-3010.2000.00083.x.
98. H. E. Miller, F. Rigelhof, L. Marquart, A. Prakash, and M.
Kanter. Antioxidant content of whole grain breakfast cereals,
fruits and vegetables. J. Am. Coll. Nutr. 19:312S�319S (2000).
99. J. L. Slavin, D. Jacobs, and L. Marquart. Grain processing and
nutrition. Crit. Rev. Food Sci. Nutr. 40:309�326 (2000)
doi:10.1080/10408690091189176.
100. L. Chatenoud, A. Tavani, C. La Vecchia, D. R. Jacobs, Jr, E. Negri,
F. Levi, and S. Franceschi. Whole grain food intake and cancer risk.
Int. J. Cancer. 77:24�8 (1998) doi:10.1002/(SICI)1097-0215
(19980703)77:1<24::AID-IJC5>3.0.CO;2-1.
101. D. R. Jacobs, Jr, L. Marquart, J. Slavin, and L. H. Kushi.
Whole-grain intake and cancer: an expanded review and metaanalysis.
Nutr. Cancer. 30:85�96 (1998).
102. L. Marquart, K. L. Wiemer, J. M. Jones, and B. Jacob. Whole
grains health claims in the USA and other efforts to increase
whole-grain consumption. Proc. Nutr. Soc. 62:151�160 (2003)
doi:10.1079/PNS2003242.
103. M. Eastwood, and D. Kritchevsky. Dietary fiber: how did we
get where we are? Annu. Rev. Nutr. 25:1�8 (2005) doi:10.1146/
annurev.nutr.25.121304.131658.
104. A. McIntyre, P. R. Gibson, and G. P. Young. Butyrate
production from dietary fibre and protection against large
bowel cancer in a rat model. Gut. 34:386�391 (1993)
doi:10.1136/gut.34.3.386.
105. J. L. Slavin, D. Jacobs, L. Marquart, and K. Wiemer. The role of
whole grains in disease prevention. J. Am. Diet Assoc. 101:780�
5 (2001) doi:10.1016/S0002-8223(01)00194-8.
106. K. S. Ahn, G. Sethi, K. Krishnan, and B. B. Aggarwal. Gammatocotrienol
inhibits nuclear factor-kappaB signaling pathway
through inhibition of receptor-interacting protein and TAK1
leading to suppression of antiapoptotic gene products and
potentiation of apoptosis. J. Biol. Chem. 282:809�820 (2007)
doi:10.1074/jbc.M610028200.107. F. H. Sarkar, S. Adsule, S. Padhye, S. Kulkarni, and Y. Li. The
role of genistein and synthetic derivatives of isoflavone in
cancer prevention and therapy. Mini Rev. Med. Chem. 6:401�
407 (2006) doi:10.2174/138955706776361439.
108. K. W. Lee, H. J. Lee, Y. J. Surh, and C. Y. Lee. Vitamin C and
cancer chemoprevention: reappraisal. Am. J. Clin. Nutr.
78:1074�1078 (2003).
109. B. A. Ingraham, B. Bragdon, and A. Nohe. Molecular basis of
the potential of vitamin D to prevent cancer. Curr. Med. Res.
Opin. 24:139�149 (2008) doi:10.1185/030079907X253519.
110. F. W. Booth, M. V. Chakravarthy, S. E. Gordon, and E. E.
Spangenburg. Waging war on physical inactivity: using modern
molecular ammunition against an ancient enemy. J. Appl.
Physiol. 93:3�30 (2002).
111. G. A. Colditz, C. C. Cannuscio, and A. L. Frazier. Physical
activity and reduced risk of colon cancer: implications for
prevention. Cancer Causes Control. 8:649�67 (1997)
doi:10.1023/A:1018458700185.
112. A. R. Shors, C. Solomon, A. McTiernan, and E. White.
Melanoma risk in relation to height, weight, and exercise
(United States). Cancer Causes Control. 12:599�606 (2001)
doi:10.1023/A:1011211615524.
113. A. Tannenbaum, and H. Silverstone. The initiation and growth
of tumors. Introduction. I. Effects of underfeeding. Am. J.
Cancer. 38:335�350 (1940).
114. S. D. Hursting, J. A. Lavigne, D. Berrigan, S. N. Perkins, and J. C.
Barrett. Calorie restriction, aging, and cancer prevention: mechanisms
of action and applicability to humans. Annu. Rev. Med.
54:131�152 (2003) doi:10.1146/annurev.med.54.101601.152156.
115. M. H. Ross, and G. Bras. Lasting influence of early caloric
restriction on prevalence of neoplasms in the rat. J. Natl. Cancer
Inst. 47:1095�1113 (1971).
116. D. Albanes. Total calories, body weight, and tumor incidence in
mice. Cancer Res. 47:1987�92 (1987).
117. L. Gross, and Y. Dreyfuss. Reduction in the incidence of
radiation-induced tumors in rats after restriction of food intake.
Proc. Natl. Acad. Sci. U S A. 81:7596�7598 (1984) doi:10.1073/
pnas.81.23.7596.
118. L. Gross, and Y. Dreyfuss. Prevention of spontaneous and
radiation-induced tumors in rats by reduction of food intake.
Proc. Natl. Acad. Sci. U S A. 87:6795�6797 (1990) doi:10.1073/
pnas.87.17.6795.
119. K. Yoshida, T. Inoue, K. Nojima, Y. Hirabayashi, and T. Sado.
Calorie restriction reduces the incidence of myeloid leukemia
induced by a single whole-body radiation in C3H/He mice.
Proc. Natl. Acad. Sci. U S A. 94:2615�2619 (1997) doi:10.1073/
pnas.94.6.2615.
120. V. D. Longo, and C. E. Finch. Evolutionary medicine: From
dwarf model systems to healthy centenarians? Science.
299:1342�1346 (2003) doi:10.1126/science.1077991

blank
Close Accordion

Excessive Weight Gain, Obesity, And Cancer

Excessive Weight Gain, Obesity, And Cancer

Opportunities For Clinical Intervention

Even though the effects of overweight and obesity on diabetes, cardiovascular disease, all-cause mortality, and other health outcomes are widely known, there is less awareness that overweight, obesity, and weight gain are associated with an increased risk of certain cancers. A recent review of more than 1000 studies concluded that sufficient evidence existed to link weight gain, overweight, and obesity with 13 cancers, including adenocarcinoma of the esophagus; cancers of the gastric cardia, colon and rectum, liver, gallbladder, pancreas, corpus uteri, ovary, kidney, and thyroid; postmenopausal female breast cancer; meningioma; and multiple myeloma.1�An 18-year follow-up of almost 93?000 women in the Nurses� Health Study revealed a dose-response association of weight gain and obesity with several cancers.2

Obesity Increase

obesity man eating oversized burger outside el paso txThe prevalence of obesity in the United States has been increasing for almost 50 years. Currently, more than two-thirds of adults and almost one-third of children and adolescents are overweight or obese. Youths who are obese are more likely to be obese as adults, compounding their risk for health consequences such as cardiovascular disease, diabetes, and cancer. Trends in many of the health consequences of overweight and obesity (such as type 2 diabetes and coronary heart disease) also are increasing, coinciding with prior trends in rates of obesity. Furthermore, the sequelae of these diseases are related to the severity of obesity in a dose-response fashion.2�It is therefore not surprising that obesity accounts for a significant portion of health care costs.

Cancers

obesity cancer-cells microsope el paso tx

A report released on October 3, 2017, by the US Centers for Disease Control and Prevention assessed the incidence of the 13 cancers associated with overweight and obesity in 2014 and the trends in these cancers over the 10-year period from 2005 to 2014.3�In 2014, more than 630?000 people were diagnosed as having a cancer associated with overweight and obesity, comprising more than 55% of all cancers diagnosed among women and 24% of cancers among men. Most notable was the finding that cancers related to overweight and obesity were increasingly diagnosed among younger people.

obesity man sits at beach el paso txFrom 2005 to 2014, there was a 1.4% annual increase in cancers related to overweight and obesity among individuals aged 20 to 49 years and a 0.4% increase in these cancers among individuals aged 50 to 64 years. For example, if cancer rates had stayed the same in 2014 as they were in 2005, there would have been 43?000 fewer cases of colorectal cancer but 33?000 more cases of other cancers related to overweight and obesity. Nearly half of all cancers in people younger than 65 years were associated with overweight and obesity. Overweight and obesity among younger people may exact a toll on individuals� health earlier in their lifetimes.2�Given the time lag between exposure to cancer risk factors and cancer diagnosis, the high prevalence of overweight and obesity among adults, children, and adolescents may forecast additional increases in the incidence of cancers related to overweight and obesity.

Clinical Intervention

obesity doctor in surgery room el paso tx

Since the release of the landmark 1964 surgeon general�s report on the health consequences of smoking, clinicians have counseled their patients to avoid tobacco and on methods to quit and provided referrals to effective programs to reduce their risk of chronic diseases including cancer. These efforts, coupled with comprehensive public health and policy approaches to reduce tobacco use, have been effective�cigarette smoking is at an all-time low. Similar efforts are warranted to prevent excessive weight gain and treat children, adolescents, and adults who are overweight or obese. Clinician referral to intense, multicomponent behavioral intervention programs to help patients with obesity lose weight can be an important starting point in improving a patient�s health and preventing diseases associatedwith obesity. The benefits of maintaining a healthy weight throughout life include improvements in a wide variety of health outcomes, including cancer. There is emerging but very preliminary data that some of these cancer benefits may be achieved following weight loss among people with overweight or obesity.4

The US Preventive Services Task Force (USPSTF)

obesity woman doctors office blood pressure taken el paso txThe US Preventive Services Task Force (USPSTF) recommends screening for obesity and intensive behavioral interventions delivered over 12 to 16 visits for adults and 26 or more visits for children and adolescents with obesity.5,6�Measuring patients� weight, height, and body mass index (BMI), consistent with USPSTF recommendations, and counseling patients about maintaining a healthy weight can establish a foundation for preventive care in clinical care settings. Scientific data continue to emerge about the negative health effects of weight gain, including an increased risk of cancer.1�Tracking patients� weight over time can identify those who could benefit from counseling and referral early and help them avoid additional weight gain. Yet less than half of primary care physicians regularly assess the BMI of their adult, child, and adolescent patients. Encouraging discussions about weight management in multiple health care settings, including physicians� offices, clinics, emergency departments, and hospitals, can provide multiple opportunities for patients and reinforce messages across contexts and care environments.

Weight Loss Programs

obesity young men working out in gym el paso txImplementation of clinical interventions, including screening, counseling, and referral, has major challenges. Since 2011, Medicare has covered behavioral counseling sessions for weight loss in primary care settings. However, the benefit has not been widely utilized.7�Whether the lack of utilization is a consequence of lack of clinician or patient knowledge or for other reasons remains uncertain. Few medical schools and residency programs provide adequate training in prevention and management of obesity or in understanding how to make referrals to such services. Obesity is a highly stigmatized condition; many clinicians find it difficult to initiate a conversation about obesity with patients, and some may inadvertently use alienating language when they do. Studies indicate that patients with obesity prefer the use of terms such as�unhealthy weight�or�increased BMI�rather than�overweight�or�obesity�and�improved nutrition and physical activity�rather than�diet and exercise.8�However, it is unknown if switching to these terms will lead to more effective behavioral counseling. Effective clinical decision support tools to measure BMI and guide physicians through referral and counseling interventions can provide clinicians needed support within the patient-clinician encounter. Inclusion of recently developed competencies for prevention and management of obesity into the curricula of health care professionals may improve their ability to deliver effective care. Because few primary care clinicians are trained in behavior change strategies like cognitive behavioral therapy or motivational interviewing, other trained health care professionals, such as nurses, pharmacists, psychologists, and dietitians could assist by providing counseling and appropriate referrals and help people manage their own health.

woman being tempted devil angel shoulder cake fruit obesity el paso txAchieving sustainable weight loss requires comprehensive strategies that support patients� efforts to make significant lifestyle changes. The availability of clinical and community programs and services to which to refer patients is critically important. Although such programs are available in some communities, there are gaps in availability. Furthermore, even when these programs are available, enhancing linkages between clinical and community care could improve patients� access. Linking community obesity prevention, weight management, and physical activity programs with clinical services can connect people to valuable prevention and intervention resources in the communities where they live, work, and play. Such linkages can give individuals the encouragement they need for the lifestyle changes that maintain or improve their health.

two men stomach cut out healthy obesity unhealthy el paso txThe high prevalence of overweight and obesity in the United States will continue to contribute to increases in health consequences related to obesity, including cancer. Nonetheless, cancer is not inevitable; it is possible that many cancers related to overweight and obesity could be prevented, and physicians have an important responsibility in educating patients and supporting patients� efforts to lead healthy lifestyles. It is important for all health care professionals to emphasize that along with quitting or avoiding tobacco, achieving and maintaining a healthy weight are also important for reducing the risk of cancer.

Targeting Obesity

Article Information

Greta M.�Massetti,�PhD1;�William H.�Dietz,�MD, PhD2;�Lisa C.�Richardson,�MD, MPH1

Author Affiliations

Corresponding Author:�Greta M. Massetti, PhD, Centers for Disease Control and Prevention, 4770 Buford Hwy NE, Atlanta, GA 30341 (gmassetti@cdc.gov).

Conflict of Interest Disclosures:�All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflict of Interest. Dr Dietz reports receipt of scientific advisory board fees from Weight Watchers and consulting fees from RTI. No other disclosures were reported.

Disclaimer:�The findings and conclusions in this report are those of the authors and not necessarily the official position of the Centers for Disease Control and Prevention.

References

1. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K; International Agency for Research on Cancer Handbook Working Group. Body fatness and cancer�viewpoint of the IARC Working Group. N Engl J Med. 2016;375(8):794-798. PubMed Article

2. Zheng Y, Manson JE, Yuan C, et al. Associations of weight gain from early to middle adulthood with major health outcomes later in life. JAMA. 2017;318(3):255-269. PubMed Article

3. Steele CB, Thomas CC, Henley SJ, et al. Vital Signs: Trends in Incidence of Cancers Related to Overweight and Obesity�United States, 2005-2014. October 3, 2017. https://www.cdc.gov/mmwr/volumes/66/wr/mm6639e1.htm?s_cid=mm6639e1_w.

4. Byers T, Sedjo RL. Does intentional weight loss reduce cancer risk? Diabetes Obes Metab. 2011;13(12):1063-1072. PubMed Article

5. Grossman DC, Bibbins-Domingo K, Curry SJ, et al; US Preventive Services Task Force. Screening for obesity in children and adolescents: US Preventive Services Task Force recommendation statement. JAMA. 2017;317(23):2417-2426. PubMed Article

6. US Preventive Services Task Force. Final Recommendation Statement: Obesity in Adults: Screening and Management. December 2016. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/obesity-in-adults-screening-and-management. Accessed September 21, 2017.

7. Batsis JA, Bynum JPW. Uptake of the centers for Medicare and Medicaid obesity benefit: 2012-2013. Obesity (Silver Spring). 2016;24(9):1983-1988. PubMed Article

8. Puhl R, Peterson JL, Luedicke J. Motivating or stigmatizing? public perceptions of weight-related language used by health providers. Int J Obes (Lond). 2013;37(4):612-619. PubMed Article

Ketogenic Diet: Preventive for Insulin Resistance and Cancer? | Nutrition

Ketogenic Diet: Preventive for Insulin Resistance and Cancer? | Nutrition

Only about 5 to 10 percent of cancer is hereditary, although most cancer scientists have thought that cancer was a disease, states Dr D’Agostino.

 

A metabolic disorder is one that interrupts normal metabolism, the process of converting food to energy on a cellular level. The mitochondria create the energy that our cells will need to perform their job, and these are usually known as the powerhouses of the cells.

 

When carbohydrates (composed of glucose) are consumed, they cause the blood glucose levels to rise. The hormone insulin, responsible for regulating energy use, is secreted by the pancreas because it damages the structure of all proteins, as a high blood sugar concentration is toxic for human tissues.

 

Based on Dr Fettke, we could simply metabolise about one teaspoon (4 grams) of glucose at once and the remainder is stored in the liver and muscles as glycogen, or if this cannot happen, it’s stored as fat.

 

The longer carbs are ingested, the more glucose is produced, the more our body becomes resistant.
Insulin resistance occurs when the body does not respond to insulin properly. This results in increased blood glucose levels, which can not be saved in muscles or the liver must store it as fat, as discussed by Prof Noakes.

 

Relation of Insulin and Health

 

Insulin is consequently the fat storing hormone, which leads to an expanding waist. In case a high carb diet is followed, and if unchecked, it can cause obesity, metabolic syndrome (a combination of hypertension, obesity and hypertension) and to type 2 Diabetes.

 

The long-term impairment which occurs in Diabetes is because of the effect of always high blood glucose levels on a lot of different organs. If blood glucose levels are high, so too will insulin amounts be, and will consequently add to the damage.

 

“The more I read the more I’m convinced of the connection between diet and cancer. A lot hinges on stimulating factors involved in metabolism and cellular division, says Dr Gary Fettkesaid

 

In his study, Dr Elio Riboli notes the higher risk of late onset breast cancer, colon, rectum, endometrial, oesophageal and kidney disorders together with obesity. He explains the link between endometrial cancer and obesity: “Essentially, endometrial cancer is quite closely connected with oestrogen levels. So the tissue there is, the more oestrogens. So there are two outcomes. One is that in the obese, oestrogens are produced by the tissue, converts androgens to oestrogens. The second one is that down-regulating sex hormone binding globulin, insulin, makes oestrogen more bioavailable.

 

According to Dr Gary Fettke, in his lecture at the LCHF Convention before this season, cancer could be tied up with sugar metabolism. Cancer cells cannot use any additional fuel for growth, except for sugar. Without sugar they starve to death. This theory is based upon the Warburg effect, by Dr Otto Warburg, who won the 1931 Nobel Prize for discovering aerobic glycolysis – a flaw in subcutaneous sugar metabolism which diverts glucose away from energy production to cell development and causes fermentation of sugar. In other words, he discovered that cancer cells thrive on glucose and have mitochondria. Dr Gary Fettke also thinks that the problem with modern cancer treatment is that it ignores the glucose metabolism.

 

“We also haven’t fully recognised the institution of diet in the causation of cancer. The problem is sugar, especially fructose, refined fats and polyunsaturated seed oils. The modern diet is inflammatory and it generates masses of oxygen free radicals.”

 

Ketogenic Diet Health Benefits

 

A low carb, high fat Ketogenic diet (that is in nature the Banting diet, but with carb consumption below 25g per day) has successfully treated many different ailments like obesity, epilepsy, Diabetes, Alzheimer’s and cardiovascular disease. Dr Seyfried requires it a single metabolic procedure for a profusion of ailments that are distinct.

 

By maintaining carbs below 25g a day, your system moves from a carb burning state to a fat burning state. Ketones are formed when the liver for energy breaks down fatty acids. Ketosis is reached when ketones are formed through withdrawal of carbs within the body. These compounds are generated throughout metabolism — and are a sign that your body is presently using fat for energy. This process forces the body. Prof Noakes explains this in more detail in the Beginner Banting Online Program, in which you may find the tools to stick to a way of life.

 

“Virtually all the wholesome cells in our body have the metabolic versatility to utilize glucose, fat and ketones to survive, but cancer cells lack this metabolic versatility and require large quantities of sugar and can’t survive on ketones. Therefore by limiting carbohydrates, we could reduce insulin and glucose, and thus limit the key fuel for cancer cell growth.” Says Dr Seyfried. Dr Gary Fettke has a vested interest in this study as he had brain cancer 15 decades ago. He switched to a diet plan and shattered the cancer.

 

Prof Noakes says, “When fighting cancer, just the finest will do. Grass-fed beef, pasture-reared chickens, organic vegetables, etc.. Since hormones and tainted foods have been fed to animals, pesticides sprayed on veg and genetically modified soya and corn is routinely fed to cows and livestock, one must be dedicated to quality in order to avoid the dangers of the substances, highly carcinogenic independently.”

 

What to eat and drink on a Ketogenic diet

 

  • Animal protein
  • Saturated fat
  • Olive oil
  • Avocado
  • Above the ground vegetables
  • Water

 

What to avoid on a Ketogenic diet

 

  • Processed food
  • Fizzy drinks
  • Toxic oils
  • Processed meat
  • Fast food

 

Cancer Fighting Foods

 

  • Tomatoes: cooking enhances cancer-fighting and anti inflammatory properties. Lycopene was found to prevent cancer cell growth in a study in Cancer and Nutrition.
  • Chilli: capsaicin that gives chillies their powerful, spicy personality is anti-bacterial, anti-carcinogenic and anti-diabetic.
  • Cruciferous vegetables: such as cabbage, cauliflower, broccoli, spinach, Brussels sprouts and kale have powerful anti-carcinogens. Cabbage in particular contain anti-oxidants known to help protect against prostate, colon and breast cancers. Broccoli is the only one having a sizable quantity of sulforaphane, an especially potent chemical that boosts the body enzymes and flushes compounds out .
  • Mushrooms: include the amino acid ergothioneine, which is an anti-oxidant and an anti-inflammatory, it protects against free radicals and boosts the immune system.
  • Aubergine: that the epidermis is rich in anti-oxidants known as anthocyanins, which are believed to fight cancer, inflammation, aging and neurological diseases.
  • Turmeric: includes curcumin that’s a powerful anti-oxidant and anti inflammatory. According to Cancer Research UK, it seems to have the ability to kill cancer cells and stop more from growing. It’s the very best consequences on breast cancer, bowel cancer, stomach cancer and skin cancer cells.
  • Berries: the idea of berries as anticarcinogens began in the late 1980s, when it was discovered that berries, and specifically black peppers, comprised ellagic acid, which is believed to inhibited the genesis of tumours.
  • Garlic: belongs to the Allium class of bulb-shaped plants, which also includes onions, chives, leeks, and scallions. It’s an strong and excellent neutraliser of free radicals. It contains good levels of selenium and, in several studies, selenium has been shown to decrease cancers. Phytochemicals in garlic have been found to stop the formation of nitrosamines, carcinogens formed in the stomach.

 

In summary, from the evidence that we have collected from all of the various sources, it’s obvious to see that the link between diet and health is a serious one and that what we consume really has an impact in the long term. Dr D’Agostino goes as far as to state, “let food be thy medicine.”

 

The scope of our information is limited to chiropractic and spinal injuries and conditions. To discuss options on the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .�
 

By Dr. Alex Jimenez

 

Additional Topics: Wellness

 

Overall health and wellness are essential towards maintaining the proper mental and physical balance in the body. From eating a balanced nutrition as well as exercising and participating in physical activities, to sleeping a healthy amount of time on a regular basis, following the best health and wellness tips can ultimately help maintain overall well-being. Eating plenty of fruits and vegetables can go a long way towards helping people become healthy.

blog picture of cartoon paperboy big news

 

TRENDING TOPIC: EXTRA EXTRA: New PUSH 24/7�? Fitness Center

 

 

Beating Cancer Twice Inspired Me to Become a Fitness Instructor

Beating Cancer Twice Inspired Me to Become a Fitness Instructor

The first sign was itchy skin. My thighs itched. My belly itched. Everything itched. I couldn’t see any rashes or dry skin, but after two months, the sensation got so bad that it distracted me at work.

I finally went to a dermatologist in December 2007. We considered potential explanations. Could it be eczema? Probably not; I showed none of the classic markers of the disorder. At the end of the appointment, I mentioned that I had a lump above my collarbone. It might be getting bigger, I told her, but I wasn’t sure.

She examined the bump and told me it was an enlarged lymph node, a gland that helps the body fight off infections. She advised me to see a general practitioner for a full checkup. She even called me a few times the following week to remind me. 

RELATED: 6 Things Your Dermatologist Wants You to Know About Skin Cancer

So I went to a general physician to have blood work done and take a chest x-ray. Then came additional tests, including a tissue biopsy of the lump. That biopsy confirmed the last thing I expected: I had stage 2A Hodgkin’s lymphoma, a blood cancer that often strikes adults in their 20s and 30s. Itchy skin, it turns out, can be a symptom.

I collapsed into my mom’s arms when I got the diagnosis. “I just don’t want to die,” I told her. I was 23, and I had so much more life to live.

The battle begins

I started chemotherapy two weeks later in my doctor’s office, enduring 12 treatments over six months. I’d get the drugs every other Thursday and take off work the following Monday, when the steroids that were supposed to ease side effects like nausea and pain wore off. Apart from that—and the wig I wore to conceal my bald head—I kept my life normal. I went my job as a fundraising event planner and met friends for dinner.

By summer, I was in remission. Yet I wasn’t feeling like my old self, and I knew I wanted to get strong again. When two friends told me they were running the Nike Women’s Marathon in San Francisco in my honor (fundraising for the Leukemia & Lymphoma Society), I was moved and motivated. With my doctor’s okay, I started to train for the Disney Half Marathon in Orlando in January 2009.

RELATED: 11 Training Tips for Running Your First Half-Marathon

I admit it was a little crazy. I’d been a runner pre-cancer, but I had never attempted a race longer than 10K. Still, I did it—I ran the half in two hours and eight minutes. Victory, right? Not quite. The weekend of my half-marathon, I noticed a familiar feeling near my collarbone. Could the lump be coming back? 

Returning to normal life in remission

I should mention that coincidentally, I’d recently started working in the fundraising department at Memorial Sloan Kettering Cancer Center (MSKCC), a top cancer hospital that my doctor was affiliated with. I wore my wig when I interviewed at Memorial in September 2008, but I didn’t mention that I had been diagnosed with cancer less than a year earlier. I wanted to be hired because I had the skills they were looking for, not my health history. Luckily, I got the job. But right after I ran my half in January, my doctor confirmed that my Hodgkin’s lymphoma was back. 

Lauren vs. cancer: round two

My doctors told me that treatment would be more aggressive the second time around, and I had to be admitted into the hospital for most of it: two preconditioning chemotherapy treatments were followed by two weeks of radiation followed by four-day rounds of high-dose chemo. “Uncomfortable” doesn’t  begin to describe the high fevers I struggled with and such severe throat pain that it hurt to eat. 

RELATED: 14 Ways to Soothe a Sore Throat 

I also underwent a stem cell transplant: a catheter transfers my own cells, collected by medical staffers weeks earlier, back into my body. The hope was that the newly transferred cells would prompt my system to produce healthy new blood cells. It’s a milestone; people in the medical world call the date of your stem cell transplant your second birthday. I celebrated my 25th birthday in the hospital on April 17. A week later, I had my ‘second birthday’ when I got my transplant.

A life dedicated to fitness 

I left the hospital in May and focused my life on recovery and getting strong again. I’ve always loved trying new classes and getting better at old ones. After all I’d been through, working out felt even more rewarding. Nearly every Saturday for the next five years, I’d be at Core Fusion Barre class at Exhale or sweating it out at SoulCycle. 

My teachers inspired me to develop a level of strength I didn’t know I had, and the thrill I felt when I realized I was getting better motivated me. With time, I made the decision to devote my life to inspiring others through fitness. In fall 2014, I signed up for barre teacher training with Exhale. Two hundred hours later, I was certified.

To get our best wellness advice delivered to you inbox, sign up for the Healthy Living newsletter

In January 2015, I left the security of a full-time job and founded Chi Chi Life. This is my way of pursuing fitness while keeping up my love for fundraising, event planning, and cancer advocacy. I teach barre at Exhale and Pilates and TRX classes at Flex Studios in New York City while also working with clients to plan philanthropic events. 

For me, fitness is all about community and connection. I’ve run several half marathons since my cancer’s been in remission, raising more than $75,000 for causes I’m passionate about. I even ran the New York City Marathon, which took me past the Memorial Sloan Kettering Cancer Center building. I wish there were words to capture what it felt like to run past the place that saved my life—and helped me discover my life’s mission.

8 Quick Ways to Slash Heart, Cancer, and Diabetes Risk

8 Quick Ways to Slash Heart, Cancer, and Diabetes Risk

“Eat a healthy diet” and “exercise for at least 30 minutes three times a week” are the two top suggestions from experts on how to stay youthful and live a long, healthy life. Unfortunately, that excellent advice can often seem overwhelming to novices who are trying to improve their health.

Where do you start? Are there easy ways to boost your health and keep aging at bay? Fortunately, there are quick, dead-simple things that clinical studies show you can do in less time than it takes to eat a cheeseburger. They include:

• Drink a cup of coffee. When the Journal of the American Medical Association reviewed a series of studies, they found that regular coffee drinkers had a lower risk of developing Type 2 diabetes than those who avoided it. They found that those who drank four to six cups a day cut their risk 28 percent, and people who drank more than six cups reduced their risk by 35 percent.

The good news about coffee keeps pouring in:  A European study found that drinking three cups of coffee daily slashes the risk of developing Alzheimer’s, and a study published in The Journal of Alzheimer’s Disease found that drinking three cups of coffee daily can help forestall Alzheimer’s in people who are already having memory problems.

There’s also good news on the war against cancer. A study from Harvard Medical School found that men who drank the most coffee slashed their risk of developing the fastest growing and most difficult to treat prostate cancers by more than half when compared to men who drank no coffee. Men who drank the most coffee — six or more cups daily — reduced their risk by 60 percent. Another study found that people who drank up to three cups of coffee daily slashed their risk of liver cancer by 55 percent.

The latest news, published in The American Journal of Clinical Nutrition found that people 65 years and older who drank four or more cups of coffee daily lowered their risk of heart disease by 53 percent.

•  Get enough vitamin D. Multiple studies show that a deficiency of vitamin D raises the risk of cardiovascular disease, diabetes, multiple sclerosis, osteoporosis, depression, and several cancers. One study found genetic markers that indicated the difference between the highest and lowest levels of vitamin D equaled five years of aging. The government recommends 400 I.U. daily, but many experts believe much more — 1,000 I.U. to 2,000 I.U —  is needed for optimal health.

• Pour a glass of red wine. A few glasses of red wine every week protect against many ailments of aging such as Alzheimer’s, cardiovascular disease, cancer, and Type 2 diabetes. It prevents heart disease by increasing levels of HDL — the good cholesterol — and guards arteries against damage. Red wine slashes the risk of some cancers, including lung and colon, by as much as two-thirds.

A recent study published in The New England Journal of Medicine found that women who drank moderately (about one drink a day) reduced their risk of mental decline by 23 percent when compared to women who were teetotalers.

 Researchers believe one of the main active ingredients in red wine is resveratrol,  a compound found in the skin of red grapes that acts as an antioxidant and is anti-inflammatory. Resveratrol is also available as a dietary supplement.

Take a daily aspirin. People take a low-dose aspirin daily to ward off heart disease, but studies have shown that the 100-year-old wonder drug also helps prevent many types of cancer. A daily low-dose aspirin can cut the risk of breast cancer and deadly melanoma skin cancer by up to 30 percent, gastrointestinal cancers and colorectal cancers by 38 percent, and lung cancer by up to 62 percent.

A new study from the University of Oxford found that a daily aspirin reduced the risk of developing cancer of any kind by about 25 percent when compared to controls who didn’t take aspirin. After five years, the risk of dying in the group taking aspirin was reduced by 37 percent. Aspirin also helps keep aging brains healthy, according to Swedish research that studied women aged 70 to 92.

• Sip green tea. People who drink more than three cups of green tea each day live longer, according to a Japanese study of more than 40,000 people. Study participants who drank the most tea — five or more cups a day — were the least likely to die during the 11-year follow up. Green and white teas contain generous amounts of EGCG, a powerful antioxidant linked to a lower risk of heart disease, Alzheimer’s disease, and numerous types of cancer. Catechins, which are antioxidant compounds found in green tea, may also protect aging eyes from glaucoma.

• Eat fish. Choosing fish over beef or pork twice a week can give your health a big boost. A study published in the journal Neurology found that seniors whose diets were rich in omega-3 fatty acids had lower blood levels of beta-amyloid, a protein that’s deposited as plaques in the brains of people with Alzheimer’s disease, and another study found fish oil reduced by 26 percent the risk of brain lesions that cause dementia. Additional studies have found that eating fish lowers the risk of Type 2 diabetes, arthritis, prostate cancer, obesity, and heart disease.

Dance. A study at Albert Einstein College of Medicine found that while reading reduced the risk of dementia in those 75 years and older, frequent dancing cut the risk by 76 percent — more than any other activity studied, mental or physical. Experts believe dancing is so effective because it combines intense mental and physical activity.

An Italian study found that people suffering from heart failure who waltzed significantly improved their breathing and quality of life when compared to those who biked or hiked. Dancing also reduces stress, depression, and obesity while it aids balance, increases energy, and helps control weight.

• Nibble on chocolate. Studies show that chocolate increases brain function and lowers blood pressure. A study at Harvard Medical School found that older people who ate chocolate every day improved their thinking skills as well as blood flow to the brain, and a German study found that small amounts of chocolate daily could reduce the risk of heart attack and stroke by almost 40 percent. Most experts recommend 1 to 1.5 ounces of dark chocolate.

Turmeric Kills Nearly All Forms Of Cancer Cells

Turmeric Kills Nearly All Forms Of Cancer Cells

The ability of turmeric to fight cancer has been extensively researched. In fact, over 1,500 published studies show that curcumin, turmeric�s active ingredient, is an effective treatment for over 100 different types of cancer.

The fact that mainstream medicine hasn�t embraced turmeric as a non-toxic cancer therapy is nothing short of outrageous. But a new study, in which curcumin outperformed conventional chemotherapy drugs, may finally bring turmeric the recognition it deserves.

 

turmeric

Turmeric Gains Popularity From Growing Awareness Of Chemotherapy & Side Effects

Chemotherapy targets cancer cells as foreign invaders to be eliminated � an approach that ignores the root causes of the disease, and doesn�t help to create an �anticancer� environment in the body. Toxic chemotherapy drugs � which kill healthy cells and cause debilitating side effects � are not very effective against cancer stem cells, the �mother cells� that regulate the growth of tumors.

In fact, the result of these toxic drugs is to make the body even more susceptible to the cancer stem cells � spurring them to create even more treatment-resistant cells.

However, chemotherapy does succeed in killing significant amounts of cancer cells, and this is not to say it should never be used. But, the opinion of many integrative healthcare professionals is that it should be used as a last resort, not a first line of defense � especially when safer, non-toxic options are available.

Curcumin Makes Chemotherapy Safer & More Effective

In a 2015 study published in Cancer Letters, curcumin was tested in conjunction with the chemotherapy drugs 5-fluoroucil and oxaliplatin against colorectal cancer. Adding curcumin to the regimen improved the efficacy of the drugs � the curcumin inhibited cancer cell growth and even increased apoptosis, or cancer cell suicide.

Even more impressive, the curcumin appeared to help the chemo drugs specifically target cancer stem cells, reinforcing the drugs� cancer-fighting abilities while lessening the side effects � including the neuropathies that can be caused by oxaliplatin. Side effects from curcumin � on the other hand � were minimal, involving mild gastrointestinal upset and dry mouth. Researchers concluded that curcumin is a �safe and tolerable adjunct� treatment.

But this wasn�t even the most significant result of the study.

Stunning Finding: Curcumin Outperformed Chemotherapy Drugs

In a small subset of patients, curcumin alone was found to be more effective in reducing overall cancer cells and cancer stem cells than the pair of chemo drugs alone. In other words, curcumin went head-to-head with chemo drugs and outperformed them � a truly astonishing result.

Researchers credited curcumin�s multiple methods of action with its success. Curcumin not only directly killed cancer cells, but also induced apoptosis, inhibited the growth of new cancer cells on a genetic level, and prevented blood supply from reaching new tumors.

All this, while promoting health with beneficial anti-inflammatory, antioxidant and hormone-balancing properties.

Extensive Studies Attest To Curcumin�s Ability To Fight Many Types Of Cancer

As the researchers noted, clinical trials of curcumin in an oncology setting have targeted many types of cancer, including colorectal, pancreatic, breast and blood cancers.

In one study, colorectal cancer patients who were given 1,080 mgs of curcumin daily showed an increase in the amount of dying cancer cells, a reduction of inflammation, improved body weight, and higher gene expression indicating suppression of cancer.

In another study published in Nutrition Research, curcumin-supplemented lab animals showed a 40 percent decrease in the development of colon tumors. These results are supported by an animal model of colon cancer in which curcumin improved survival rate and colon health by completely eliminating cancerous tumors.

In yet another study, patients with pancreatic cancer who were given 8,000 mgs of curcumin a day showed increased survival time along with significant reductions in tumor size � in one case, up to 73 percent.

And, finally, in a study involving prostate cancer, curcumin was shown to cut in half the growth rate of prostate-specific androgen, a marker of tumor progression.

Turmeric Is Still Unapproved & Unacknowledged By Conventional Medicine

In spite of its proven results, turmeric is not approved by the FDA for cancer treatment � and does not enjoy mainstream acceptance in the conventional medical community. The reason, many say, is financial � with hundreds of millions of dollars invested in clinical trials, and massive profits to be made, big pharma doesn�t have much incentive to develop a treatment from a common kitchen spice.

In fact, the industry lobbies to make treatment of cancer by alternative means a criminal offense.

Having said that, we naturally suggest you talk to a trusted medical professional before using turmeric � for any reason � and, don�t stop taking prescribed medication unless advised by your physician.

It should be noted that in the past, turmeric�s therapeutic potential has been limited by its poor bioavailability � the fact that the body doesn�t absorb or use it effectively. But, the development of liposomalized turmeric extract has changed all that, increasing the bioavailability 10 to 20-fold and allowing the curcumin to begin its health-promoting and cancer-fighting work.

Hopefully, the research � presented in this article � will shine a light on the amazing healing potential of turmeric. We encourage every caring physician to do their own research � for the sake of their patients.

Editor�s note: I, personally, use a wonderful liposomal form of turmeric � which you can purchase here and, yes, your purchase does support our operations � at no extra cost to you.

Call Today!

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4510144
http://www.naturalhealth365.com/curcumin-prevent-cancer-1803.html

http://www.naturalhealth365.com/curcumin-cancer-cells-2009.html

Lifestyle Factors Can Increase the Risk of Developing Cancer

Lifestyle Factors Can Increase the Risk of Developing Cancer

Cancer isn’t inevitable, but many Americans don’t know that several lifestyle factors affect their risk of developing the disease, a new survey finds.
Only one in two Americans is aware that obesity can raise the risk of cancer. And fewer than half understand that alcohol, inactivity, processed meat, eating lots of red meat and low consumption of fruits and vegetables are linked to cancer risk, the researchers said.

“There is a clear crisis in cancer prevention awareness,” said Alice Bender, head of nutrition programs at the American Institute for Cancer Research.

A larger percentage of Americans mistakenly believe that stress, fatty diets and other unproven factors are linked with cancer, according to the institute’s 2017 Cancer Risk Awareness Survey.

“It’s troubling that people don’t recognize alcohol and processed meats increase cancer risk,” Bender said in an institute news release. “This suggests the established factors that do affect cancer risk are getting muddled with headlines where the research is unclear or inconclusive.”

Factors Affecting the Risk of Cancer

Highlights of the survey findings include:

  • Fewer than 40 percent of Americans know that alcohol affects cancer risk.
  • Only 40 percent know that processed meats are also associated with cancer risk.
  • Fifty percent of Americans are aware that being overweight spurs cancer risk, up from 35 percent in 2001.

Nearly one-third of common cancers in the United States could be prevented through diet, weight management and physical activity. That increases to half when factors such as not smoking and avoiding sun damage are added, according to the institute.

Research has linked alcohol to at least six cancers, including colon, breast, liver and esophageal. Studies have also shown that bacon, hot dogs and other processed meats may raise the risk of colon and stomach cancers.

Only half of Americans know that obesity increases the risk of several cancers and that a healthy weight is the second most important way — after not smoking — to reduce cancer risk, the researchers said.

“We know a lot of healthy people do get cancer and sometimes it’s easier to worry about genes or uncontrollable things rather than your everyday choices,” said Bender. “But the research says that being physically active, staying a healthy weight, and eating a plant-based diet has the potential to prevent hundreds of thousands of cancer cases each year,” Bender aded. “It’s a powerful message.”

SOURCE: American Institute for Cancer Research, news release, Feb. 1, 2017

News stories are written and provided by HealthDay and do not reflect federal policy, the views of MedlinePlus, the National Library of Medicine, the National Institutes of Health, or the U.S. Department of Health and Human Services.

The scope of our information is limited to chiropractic and spinal injuries and conditions. To discuss options on the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .�

Additional Topics: Whole Body Wellness

Following a balanced nutrition as well as engaging in regular physical activity and sleeping properly are all proper lifestyle habits which can help increase and maintain overall health and wellness. Many common complications associated with improper lifestyle habits, such as obesity, diabetes, heart disease and cancer, however, the risk of developing these can be prevented with a few lifestyle changes. In addition, visiting a chiropractor and receiving chiropractic care can help maintain and improve the overall health of the spine as well as its surrounding structures.

 

blog picture of cartoon paperboy big news

 

TRENDING TOPIC: EXTRA EXTRA: New PUSH 24/7�? Fitness Center

 

 

TTUHSC El Paso Hosts Colon Cancer Awareness Events

TTUHSC El Paso Hosts Colon Cancer Awareness Events

Related Articles

In honor of Colorectal Cancer Awareness Month this March, the Against Colorectal Cancer in Our Neighborhoods (ACCION) program is teaming up with community partners to raise awareness about colorectal cancer and to encourage El Pasoans to get tested for the disease.

ACCION is a cancer prevention program at Texas Tech University Health Sciences Center El Paso (TTUHSC El Paso) that offers no-cost screenings to qualifying El Paso residents.

Even though colon cancer is easily prevented with a simple screening test, this cancer is the second leading cancer killer in the U.S. Doctors encourage adults age 50 and older to be regularly tested for colon cancer, but many El Pasoans do not follow these guidelines.

In fact, El Paso has one of the lowest colon cancer screening rates in Texas. According to theTexas Department of State Health Services, only 54 percent of qualifying residents get tested for the cancer, compared to 66 percent of the rest of the U.S.

On March 15, TTUHSC El Paso will join efforts with El Pasoan’s Fighting Hunger and New Mexico State University to conduct colorectal cancer education at Guillen Middle School. The event will include a food pantry distribution and NMSU’s giant, inflatable colon for families to tour.

On March 23, TTUHSC El Paso’s ACCION team will visit the San Jacinto Adult Learning Center to educate some 150 adult students about colorectal cancer. Those who are eligible for colon cancer testing will be offered a free screening through the program.

A former ACCION participant will be on-hand to discuss the program and to encourage students to get screened, thereby lowering their risk of colon cancer. NMSU will assist with cancer education and have their giant colon on display.

What: Colon Cancer Awareness Month Events

When: 3 to 5 p.m. Tuesday, March 15 and 8 to 11 a.m. Wednesday, March 23

Where: Guillen Middle School, located at 900 S. Cotton Street, and the San Jacinto Adult Learning Center, located at 1216 Olive Avenue

Exercise Can Help Counter Cancer-Associated Fatigue

Exercise Can Help Counter Cancer-Associated Fatigue

Whether from the disease itself or the treatment, cancer can be exhausting, but a new review says there are ways to beat back cancer-related fatigue.

The review included a look at 113 past studies that included more than 11,000 adult cancer patients. The researchers found that exercise and/or behavioral and educational therapy seemed to be more effective than prescription drugs for dealing with fatigue.

“Exercise and psychological treatment, and the combination of these two interventions, work the best for treating cancer-related fatigue — better than any pharmaceuticals we have tested,” noted study lead author Karen Mustian. She’s an associate professor with the University of Rochester Medical Center’s Wilmot Cancer Institute in Rochester, N.Y.

The upshot, said Mustian, is that doctors should consider exercise and psychological interventions as the “first-line therapy” instead of more medications when it comes to tackling cancer-related fatigue. The study team noted that cancer-related fatigue is a very common problem among cancer patients, both during and following treatment. The American Cancer Society describes the phenomenon as distinct from routine tiredness. Even if you get rest, you’re still tired. Your arms and legs may feel heavy. You may feel too tired to do even the simplest tasks, such as eating a meal, according to the ACS.

Beyond affecting overall quality of life, cancer-related fatigue can also interfere with a patient’s ability to continue cancer treatment itself. That may result in a poorer prognosis and, in some cases, a reduced chance for long-term survival, the study authors said.

For the study, Mustian and colleagues looked at cancer-related fatigue triggered by the onset of cancer itself, rather than as a side effect of treatment.

Almost half of the patients included in the review were women battling breast cancer. Ten studies focused solely on male patients. In all, almost 80 percent of study participants were women. Their average age was 54. The analysis excluded studies that looked at so-called complementary therapies, with an exception made for alternative exercise treatments, such as yoga or tai chi.

In addition, the research team didn’t include studies that had assessed drug treatments involving erythropoietin medications (such as epoetin alpha, brand names Procrit and Epogen). These drugs are designed to stimulate red blood cell production, and are “used primarily for treating anemia and are not recommended as a stand-alone treatment for [cancer-related fatigue] due to adverse effects,” the study authors stated.

Studies included looked at the impact of four different treatment approaches: exercise alone (including aerobic, such as walking or swimming or anaerobic, such as weight-lifting); mental health interventions aimed at providing information and/or helping patients understand and adapt to their current situation; a combination of both exercise and psychological treatment; and prescription drugs, including stimulant medications (such as modafinil, brand name Provigil) and ADHD meds (such as methylphenidate, brand name Ritalin).

All four interventions led to improvement in fatigue. But the researchers found that exercise therapy led to the best outcomes. But psychological therapies produced similarly positive results, as did treatments that integrated exercise with mental health efforts.

The team concluded that when it came to controlling cancer-related fatigue, the exercise and/or psychological therapy approaches appeared to outperform prescription drugs. Colleen Doyle is managing director of nutrition and physical activity for the ACS. She said exercise has many benefits, not just helping to ease fatigue.

“But because many people undergoing treatment do experience fatigue, it’s nice to know that there is something an individual can do to help reduce that fatigue and gain some of the many other benefits of exercise [both during and after treatment]: reduced stress, less anxiety, [and] benefits to physical functioning,” Doyle said.

But can the typical cancer patient actually handle an exercise regime? Mustian says yes.

“These are not your elite athletes or fitness buffs,” she said. Almost all of the studies focused on people who had been sedentary and were placed on a low-to-moderate intensity exercise regimen, involving activities such as yoga or resistance training. “So they are normal people who were not regular exercisers, and who were able to complete these interventions and have relief from their fatigue,” Mustian said.

Doyle said that for patients who weren’t previously active, it’s important to start slowly.

“Our recommendation for survivors is essentially avoid inactivity as best you can. There will be days when you feel like not doing much of anything, and that’s okay, but strive to do something. Even if it is gentle stretching exercises, or a five-minute walk down the block,” she advised.

Mustian stressed that relatively few studies looked at combining exercise and psychological therapy.

“So it is not as clear what the best way to combine them would be,” she noted. The researchers said more studies need to be done to explore the ideal way to integrate exercise and psychological interventions.

The study was published March 2 in JAMA Oncology.

SOURCES: Karen M. Mustian, Ph.D., M.P.H., associate professor, Wilmot Cancer Institute, department of surgery, University of Rochester Medical Center, Rochester, N.Y.; Colleen Doyle, M.S., R.D., managing director, Nutrition and Physical Activity, American Cancer Society; March 2, 2017, JAMA Oncology

The scope of our information is limited to chiropractic and spinal injuries and conditions. To discuss options on the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

Additional Topics: What is Chiropractic?

Chiropractic care is an well-known, alternative treatment option utilized to prevent, diagnose and treat a variety of injuries and conditions associated with the spine, primarily subluxations or spinal misalignments. Chiropractic focuses on restoring and maintaining the overall health and wellness of the musculoskeletal and nervous systems. Through the use of spinal adjustments and manual manipulations, a chiropractor, or doctor of chiropractic, can carefully re-align the spine, improving a patient�s strength, mobility and flexibility.

 

blog picture of cartoon paperboy big news

 

TRENDING TOPIC: EXTRA EXTRA: New PUSH 24/7�? Fitness Center

 

 

Moringa- Prevent Cancer, Diabetes, Cure Asthma, Boost Energy & Potent Natural Antibiotic

Moringa- Prevent Cancer, Diabetes, Cure Asthma, Boost Energy & Potent Natural Antibiotic

Moringa- Prevent Cancer, Diabetes, Cure Asthma, Boost Energy & Potent Natural�Antibiotic

Moringa is one of the most nutrient-dense plants on the planet. Moringa oleifera tree has been called the tree of life in many cultures around the world. It is estimated that at least 300 diseases can be cured by taking this plant along with hundreds of other health benefits, thanks to its more than 90�

Sourced through Scoop.it from: stephanieobishop.wordpress.com

View On WordPress