Journal of Postgraduate Medicine Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India ISSN: 0022-3859 EISSN: 0972-2823 Vol. 55, Num. 1, 2009, pp. 45-54

Journal of Postgraduate Medicine, Vol. 55, No. 1, January-March, 2009, pp. 45-54

Review Article

Dietary factors and cancer chemoprevention: An overview of obesity-related malignancies

Murthy NS, Mukherjee S, Ray G, Ray A

Hormel Institute, University of Minnesota, Austin, MN 55912
Correspondence Address:Hormel Institute, University of Minnesota, Austin, MN 55912, amitraym@rediffmail.com

Date of Submission: 26-Apr-2008
Date of Decision: 30-May-2008
Date of Acceptance: 30-Jul-2008

Code Number: jp09013

Abstract

Keywords: Adiponectin, adiposity, phytochemicals, primary prevention, tumor

Obesity is a serious health problem in the industrialized world. Also, similar trends have been observed in many developing countries. ^[1] Energy-dense diets with refined carbohydrates and saturated fat, and sedentary lifestyle are associated with the development of obesity. ^[2] According to the World Health Organization (WHO), currently more than 1 billion adults are overweight globally and is a major contributor to the global burden of chronic diseases and disability. Obesity is associated with a number of disorders including cardiovascular disease, hypertension, Type 2 diabetes, dyslipidemia and cancer. ^[3] Probably, a large number of cancers are linked with obesity such as cancers of the colon, breast (postmenopausal), endometrium, kidney, esophagus and gastric cardia (adenocarcinoma), gall bladder, liver, pancreas, prostate (advanced malignancy), ovary and hematopoietic tissues like non-Hodgkin′s lymphoma (NHL), multiple myeloma and leukemia. ^[4] Furthermore, it is worthy to mention that obesity may influence prognosis through various mechanisms, including co-morbidities and endocrine factors. ^[5] In addition to serve as an energy depot, adipose tissue or fat mass releases several hormone-like chemicals or adipokines, which perhaps provide a link among cancer, insulin resistance, inflammation and oxidative stress. ^[6],[7],[8] A growing body of evidence suggests that insulin resistance and associated metabolic syndrome, which appears as a complication of obesity, promotes the pathogenesis of cancer [Figure - 1]. ^[7],[9],[10]

Among adipokines, leptin and adiponectin possibly influence significantly in the etiopathogenesis of different malignant tumors. A sizable number of studies have indicated that leptin may potentiate the growth of cancer cells, whereas adiponectin appears to have an opposite effect. ^[11] With leptin, adiponectin may participate in the maintenance of energy homeostasis; obesity begins to develop when this energy regulation is disrupted. ^[12] Adiponectin′s anti-cancer properties perhaps are associated with its anti-inflammatory, anti-oxidative and insulin-sensitizing effects [Table - 1]. ^[13]

The contribution of diet and nutrition status to cancer risk has been a major focus of research as well as public health policy. Diet plays a major role in cancer etiology and its prevention. Interestingly, various studies carried out have shown that cancer is largely a preventable disease, and the incidence of cancer can be reduced substantially by means of dietary modification. ^[14] Different types of epidemiological designs such as correlation studies, observational studies, cohort, case-control studies and controlled trials in selected groups have been employed to obtain sufficient proof of causal relationships between dietary modification and cancer. This offers the prospect for initiating primary and secondary prevention measures for control and prevention of cancers.

It has been suggested that a high intake of fruits and vegetables to be a valid tool for cancer prevention. ^[15],[16] Block et al., reviewed about 200 studies of cancer and intake of fruits and vegetables. ^[17] A statistically significant protective effect of fruits and vegetables was found in 128 of 156 studies in which results were expressed in terms of relative risk. People in the lower quartile who ate the least amount of fruits and vegetables had about twice the risk compared to the subjects of the upper quartile who ate fruits and vegetables adequately. An enormous body of literature supports the recommendation for people to eat more fruits and vegetables. ^[17],[18] Although different types of fruits and vegetables have different nutrient profiles, they are generally good sources of carbohydrates, fiber and phenolic compounds apart from vitamins and minerals including calcium and iron [Table - 2].

Several studies have shown that increased consumption of fruits and vegetables was associated with body weight reduction. ^[19],[20] Like anti-cancer effects, phenolic compounds or phytochemicals present in fruits and vegetables also have been demonstrated to possess anti-obesity and lipid-lowering effects. ^[21],[22] Furthermore, phytochemicals like capsaicin, the pungent constituent of hot peppers, can enhance the expression of adiponectin gene and protein. ^[23] Interestingly, a recent report from the American Cancer Society has concluded that substantial reductions in the incidence of obesity-related cancers can be expected if the obesity epidemic can be stabilized and reversed in the coming years. ^[24] Considering the above-mentioned facts, in this review paper, we have tried to concentrate on the preventive aspects of obesity-related cancers mainly by dietary agents. For this purpose, PubMed system has been used primarily to search for the relevant papers. In the first part of this review article, we have mentioned the findings of different chemoprevention trials or dietary modification studies of leading obesity-related cancers. Finally, various dietary agents that have both anti-obesity and anti-cancer effects have been discussed.

Cancer chemoprevention trials/dietary modification studies in selected obesity-related cancers

Prostate cancer

A variety of innovative approaches to the prevention of prostate cancer are now available, including selenium, alpha-tocopherol, dietary interventions and vitamin D supplementation. Several prospective studies such as Physicians′ Health Study, Netherlands Cohort Study, Baltimore Longitudinal Study of Aging, Washington County Study, Health Professional Follow-up Study and Prospective Study have examined the role of selenium in cancer prevention, particularly for prostate cancer. ^{[25],[26],[27],[28],[29],[30]} The selenium supplementation has been found to be effective. The National Cancer Institute (NCI) organized the chemoprevention research program and began testing the first generation of promising agents in high-risk cohorts and launched the first large-scale US Phase 3 primary prevention trial, known as Prostate Cancer Prevention Trial (PCPT-1), in 18,000 average risk men treated for seven years with finasteride or placebo. ^[31] The impact of the PCPT-1 continues ^[32] and subsequent articles have addressed the increase of high-grade prostate cancers detected in the finasteride arm of the trial. ^[33] Growing evidence supports the concept of chemoprevention agent combinations and the role of selenium, lycopene, soy, green tea, anti-inflammatories and statins in prostate cancer prevention. ^{[34],[35],[36],[37]} Randomized double-blind controlled trials have also confirmed the effect of selenium supplementation in reducing risk of prostate cancer. ^[38],[39] Further, a randomized placebo-controlled trial to evaluate the supplementation of selenium (200 µg/day in the form of selenomethionine) to prevent the development of prostate cancer among men with high-grade prostatic intraepithelial neoplasia, a pre-malignant lesion, is in progress and study will be completed by 2009. ^[40]

Ansari et al., have reviewed the articles relating to intervention and clinical trials on chemoprevention of prostate cancer published in the last 20 years. ^[41] It has been reported that nutritional factors such as reduced fat intake, vitamin A, vitamin E, vitamin C, vitamin D, lycopene and selenium may have protective effect against prostate cancer. It has concluded that bioactive compounds (antioxidants) like vitamins A, C, D, E, minerals like selenium and carotenoids like lycopene can be a part of chemoprevention strategies for prostate cancer. ^[42]

Breast cancer

The only agent to have general approval for chemoprevention of breast carcinoma is tamoxifen. A reduction in the risk has been observed to an extent of 50% in high-risk women. However, tamoxifen is associated with adverse events. Adjuvant dietary modifications have also been suggested based on epidemiological and preclinical observations that link high-fat diet to mammary tumorigenesis. A diet rich in vegetables has shown a moderate protective effect in the prevention of breast cancer. ^[43] Flaxseed, the most significant source of plant lignans, and wheat bran, an excellent source of dietary fiber, have both been shown to have chemoprotective benefits in premenopausal women. ^[44] Some of these benefits have been attributed to their influence on endogenous sex hormone production and metabolism.

An Italian cohort of 8,984 women was followed for an average of 9.5 years, with 207 incident cases of breast cancer during that time. The diet patterns were analyzed in terms of salad (raw vegetables and olive oil), western (potatoes, red meat, eggs and butter), canteen foods (pasta and tomato sauce) and prudent (cooked vegetables, pulses and fish). Only salad vegetable diet pattern was associated with a significantly lower risk of breast cancer. ^[45]

The Women′s Health Initiative (WHI) study was a long-term health study that focused on strategies for preventing heart disease, breast and colorectal cancer and osteoporosis in postmenopausal women. The study included both dietary and chemoprevention interventions. The trial attempted to examine the effects of (i) a low-fat eating pattern (20% of calories from fat) with higher vegetables, fruits and fiber (ii) hormone replacement therapy and (iii) calcium and vitamin D supplementation on the prevention of cancer, cardiovascular disease and osteoporosis. The study was conducted as a randomized, controlled primary prevention trial at US clinical centers from 1993 to 2005. A total of 48,835 postmenopausal women, aged 50-79 years without prior breast cancer were enrolled. Women were randomly assigned to the dietary modification intervention group (n=19,541) or the comparison group (n=29,294). The intervention was designed to promote dietary change, reducing intake of total fat and increasing consumption of vegetables and fruit to at least five servings daily and grains to at least six servings daily. Comparison group subjects were not asked to make dietary changes. The findings of the study revealed that among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1 years average follow-up period. However, the non-significant trends were observed. This suggested that longer planned non-intervention follow-up might yield definitive comparison. ^[46]

The Nurses′ Health Study was designed as a prospective follow-up study during the year 1976 to examine the relationship between contraception and breast cancer. The study was soon expanded to include diet and nutrition, in recognition of their roles in the development of chronic disease. The study enrolled 116,000 women. With follow-up questionnaires mailed every two years, investigators have added extensive details of lifestyle practices. The relationship between use of hormones, diet, exercise, and other lifestyle practices have been related to the development of a wide range of chronic illnesses among women. Models of breast cancer have been developed based on the data from Nurses′ Health Study. The model reveals that the risk for breast cancer is set by the events of early life exposures. A relationship exists between the diet and other lifestyle factors during adolescence and the subsequent risk of breast cancer. ^[47]

Endometrial cancer

Studies revealed that high fat consumption increased endometrial cancer risk. ^[48,49] Interestingly, several case-control studies have suggested an inverse association between vegetable consumption and the risk for endometrial cancer; however, prospective cohort studies cannot find similar results. ^{[48],[50],[51],[52],[53]} After a thorough analysis of different case-control studies, both population-based and hospital-based studies, Bandera et al., observed a major preventive role of cruciferous vegetables against the risk of endometrial cancer. ^[53] Reports also suggested that soy beans and isoflavones can reduce the risk of endometrial cancer. ^[48],[54] Moreover, consumption of both fruits and vegetables was inversely associated with endometrial cancer risk in a population-based case-control study. ^[55]

Kidney cancer

Renal cell cancer (RCC) accounts for a small percentage of cancers worldwide, but its incidence rates have been steadily increasing. In the recent report of European Prospective Investigation into Cancer and Nutrition (EPIC), overall no significant associations between fruits and vegetable consumption and RCC risk were observed; however, an inverse association was found for root vegetables. ^[56] On the other hand, in a population-based prospective cohort study among Swedish women, the risk of RCC decreased with increasing intake of fruits and vegetables, particularly banana within the group of fruits, and root vegetables, white cabbage, and salad vegetables within the group of vegetables. ^[57] Similarly, a significant inverse association with RCC was observed with increasing total consumption of vegetables in a case-control study in Canada. ^[58] Significant inverse associations were noticed for females taking dark-green vegetables, cruciferous vegetables, vitamin E or calcium supplements. ^[58] Interestingly, a multi-centric case-control study conducted in Italy found a beneficial role of dietary fibers on RCC risk. ^[59]

Esophageal adenocarcinoma

The incidence of esophageal adenocarcinoma (EAC) has increased rapidly like RCC. In the EPIC cohort study conducted in 10 European countries, a possible protective role of vegetable intake against EAC was found. ^[60] Furthermore, citrus fruit consumption exhibited a protection against EAC and gastric cardia adenocarcinoma. ^[60] However, in the NIH-AARP Diet and Health Study (a prospective cohort study in the US), a significant inverse association with EAC was observed only for spinach intake. ^[61] On the other hand, in a nationwide population-based case-control study in Sweden on fruit and vegetable consumption, individuals in the highest exposure quartile (median 4.8 servings/day) versus the lowest (median 1.5 servings/day) showed approximately 50% lower risk of EAC, but no risk reduction for gastric cardia adenocarcinoma. ^[62]

Colon cancer

A joint report by the World Cancer Research Fund and American Institute of Cancer Research found convincing evidence that a high fruit and vegetable intake would reduce cancer of the colon and rectum. ^[14] On the contrary, obesity, greater adult height, frequent eating, and diets high in sugar, total and saturated fat, eggs, high alcohol intake, and processed meat, all possibly increase the risk. ^[14] A Finnish cohort study observed that high cholesterol intake was associated with increased risk of colorectal cancers, non-significant associations were found for consumption of meat and eggs. ^[63] On the other hand, Mathew et al., noticed that high intake of fish was associated with lower risk of recurrence of colorectal adenomas, which are precursors of most colorectal malignancies. ^[64] Furthermore, increased intake of dietary fiber-rich foods may decrease the risk of adenomas. ^[65],[66] A study also suggested that legume fiber may reduce colorectal cancer risk. ^[67] Like dietary fiber, calcium supplementation was shown to be associated with a significant reduction in the risk of recurrent colorectal adenomas. ^[68] Giovannucci et al., reported a substantial reduction of colon cancer risk by long-term use of multivitamins including folate. ^[69]

Non-steroidal anti-inflammatory drugs (NSAID) have been widely studied because there are a number of mechanisms through which these agents might prevent colon cancer. However, the Women′s Health Study (a randomized controlled trial) did not find any protective effect of low-dose aspirin use on the incidence of colorectal cancer. ^[70] The recent clinical guidelines prepared for the US Preventive Services Task Force have concluded that aspirin appears to be effective at reducing the incidence of colonic adenoma and colorectal cancer, especially if used in high doses for more than 10 years. ^[71] However, the possible harms of such a practice require careful consideration. ^[71]

Dietary agents that may have both anti-obesity and anti-cancer effects

Garlic: Allium vegetables, particularly garlic ( Allium sativum ), have been considered to posses medicinal qualities for a long time in human history. In fact, these common food plants are thought to have beneficial effects in a number of diseases including cancer, coronary heart disease, obesity, hypercholesterolemia, diabetes Type 2, hypertension, cataract and some gastrointestinal disorders. ^[72] Several epidemiological studies have shown a reduction of the risk of different cancers by consumption of garlic. ^{[73],[74],[75],[76]} Fresh garlic contains various organosulfur compounds, trace elements and compounds of phenolic and steroidal origin, along with carbohydrates, proteins and fiber. ^[72],[77] Organosulfur compounds from garlic, especially allicin, diallyl sulfide, diallyl disulfide and diallyl trisulfide are recognized as a group of potential chemopreventive agents. ^[78] These compounds can cause G2/M phase arrest in the proliferation of cancer cells, induction of apoptosis by altering the ratio of the Bcl-2 family of proteins and anti-angiogenic activity. ^[79] Collectively, preclinical investigations demonstrated consistently that cancer chemoprevention by garlic and related sulfur compounds is clearly evident and appears to be independent of the organ site or the carcinogen employed. ^[80]

Fenugreek: Fenugreek ( Trigonella foenum graecum ) seeds are traditionally used to treat diabetes, hypercholesterolemia, wounds, inflammation and gastrointestinal ailments. ^{[81],[82],[83]} It has been observed that the seed extract inhibited tumor cell growth and also produced a significant anti-inflammatory effect. ^[84] Furthermore, in the experimental animals, inclusion of fenugreek seed powder in the diet reduced the colon tumor incidence, decreased lipid peroxidation and increased the enzymatic activities of the antioxidant system such as glutathione peroxidase (GPx), glutathione S -transferase (GST), superoxide dismutase (SOD) and catalase. ^[85] Fenugreek seeds are a rich source of fiber and various saponins (i.e. glycosides of steroids) like different trigoneosides, diosgenin [Figure 2A] and protodioscin. ^{[81],[83],[86]} Several studies have observed anti-proliferative effects of diosgenin on different types of cancer cells. ^{[87],[88],[89]} Raju and Bird reported that the expression of 3-hydroxy-3-methylglutaryl co-enzyme (HMG-CoA) reductase, the rate-limiting enzyme of the cholesterol biosynthetic pathway, was significantly lowered by diosgenin in human colon carcinoma cells. ^[90] Nevertheless, the findings of Wang et al., both from in vivo and in vitro experiments suggest that diosgenin has an obvious anti-tumor activity. ^[91]

Green tea: The beneficial properties of green tea are mostly credited to polyphenols having powerful antioxidant properties. The polyphenols in green tea are classified as catechins. Green tea contains six primary catechin compounds: catechin, gallaogatechin, epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate (EGCG, [Figure 2B]). ^[92] Green tea also contains alkaloids including caffeine, theobromine, and theophylline. These alkaloids provide green tea′s stimulant effects. EGCG is the most studied polyphenol component in green tea. EGCG is a potent antioxidant and protects fragile DNA and cells from destructive free radicals. It has been estimated that a single cup of green tea can contain up to 200 mg of EGCG. ^[93] EGCG may have health benefit as a nutritional supplement against cancer, atherosclerosis, obesity, cardiovascular and neurodegenerative diseases. ^{[94],[95],[96],[97]}

Soy: Soy beans contain high-quality proteins and have been consumed for a long time in oriental countries. The protein content of soybean is roughly about 50%; and the predominant proteins are conglycinin (7S globulin) and glycinin (11S globulin), which comprise approximately 80% of the total proteins. ^[98],[99] Isoflavones are present in the soybean primarily as glycosides such as genistin, daidzin and glycitin; their respective aglycones are genistein, daidzein and glycitein. Usually, in common soy foods like cooked soybeans and tofu, isoflavone content is about 3 mg per gram of protein and aglycone weight is approximately 60% of the glycoside. ^[100] Apart from protein and isoflavones, soybeans also contain saponins, phytosterols, phytic acid, phospholipids, ascorbic acid, minerals and fiber. ^{[98],[99],[101]} In experimental animals, it has been observed that soy isoflavone improved the insulin sensitivity by decreasing visceral fat deposition and low-grade inflammation, ^[102] and can lower the levels of plasma cholesterol. ^[103] Moreover, results of different investigations suggest that soy protein may reduce the body fat content in obesity. ^[104,105] In some recent studies, soy food intake has been shown to be associated with a decreased risk of breast, prostate and colon cancer. ^{[106],[107],[108],[109],[110]} Both soy protein and isoflavones have revealed different anti-cancer effects such as anti-angiogenic activity, apoptosis and modulation of cell cycle progression. ^{[111],[112],[113],[114]}

Bitter melon: Bitter melon ( Momordica charantia ) contains cucurbitane-type triterpene glycosides like charantosides, alkaloids like momordicine, conjugated linolenic acid derivatives like octadecatrienoic fatty acid (9-cis, 11-trans, 13-trans/9c,11t,13t-CLN, [Figure 2C]) and proteins like MAP30. Interestingly, in several ways, the effects of bitter melon extracts are comparable to the actions of oral hypoglycemic agents such as metformin and thiazolidinedione drugs (e.g., rosiglitazone and pioglitazone). ^[115],[116] Studies observed that bitter melon inhibited adipocyte hypertrophy, decreased adiposity, lowered cholesterol and triglycerides concentrations, reduced serum glucose levels, improved insulin resistance status and increased serum adiponectin concentration. ^{[116],[117],[118],[119],[120]} It has been found that linolenic acid (9c,11t,13t-CLN), present in bitter melon seed oil, can up-regulate PPARγ and induce apoptosis in colon cancer cells. ^[121],[122] Moreover, MAP30 (Momordica protein of 30 kDa) has been shown to inhibit human breast cancer MDA-MB-231 cells in vitro and in vivo (i.e., xenograft model). ^[123] In experimental animals, extract of bitter melon inhibited the development of skin tumor, ^[124] mammary tumor ^[125] and formation of aberrant crypt foci (ACF) in the colon. ^[126]

Plant defense molecules: Plants respond to pathogenic invasion by the induction of a variety of defense mechanisms such as deposition of lignin in cell walls, phytoalexin production and synthesis of pathogenesis-related (PR) proteins. Among phytoalexins, resveratrol (trans-3,4´,5-trihydroxystilbene) [Figure 2D] has been shown to possess chemopreventive effects against different cancers. It is a polyphenolic compound (stilbenoid) found in various plants and fruits including grapes. Resveratrol inhibits the process of carcinogenesis by affecting the diverse cellular events associated with tumor initiation, promotion and progression phases and suppresses the final steps of carcinogenesis, i.e., angiogenesis and metastasis. ^[127] Furthermore, it has been demonstrated that resveratrol decreased the proliferation rate and induced apoptosis in cancer cells. ^[128],[129] Interestingly, anti-cancer effects also have been reported in case of several analogues of resveratrol such as pterostilbene [Figure 2E], piceatannol [Figure 2F] and vaticanol C. ^{[130],[131],[132],[133]} Studies have suggested that both resveratrol and pterostilbene can decrease blood lipid levels. ^[134],[135] It may be worthy to mention that resveratrol acts as an agonist of SIRT1, which regulates adiponectin biosynthesis. ^{[136],[137],[138]}

The PR proteins include different structurally and functionally unrelated proteins that have been grouped in 14 families. ^[139] The family 5 of PR proteins (i.e., PR-5) comprises thaumatin-like proteins; ^[140] because of the sequence homologies between PR-5 proteins and thaumatin, an intensely sweet-tasting protein isolated from the fruits of the West African rain forest shrub Thaumatococcus danielli , members of this family of proteins are referred to as thaumatin-like proteins. ^[141] It is worthwhile to state that natural sweet proteins like thaumatin, brazzein or monellin have the potential to replace manmade artificial sweeteners and refined sugars that are associated with various adverse effects including obesity-related problems like insulin resistance. ^[142] Thaumatin-like proteins can be classified into three groups: (i) those produced in response to pathogen infection, (ii) anti-fungal proteins present in cereal seeds, and (iii) proteins produced in response to osmotic stress, also called osmotin. ^[141] Fruits and vegetables such as grapes, tomatoes, soybeans and carrots are good sources of osmotin, which is a 24 kDa stable protein. It has been observed that osmotin can bind to PH036, a homolog of adiponectin receptor in yeast, and can induce similar signaling pathway like adiponectin via adiponectin receptor. ^[143] Study on this adiponectin receptor agonist is a promising area of cancer chemoprevention research. ^[144]

Fish: In recent time, among dietary lipids, much attention has been given to the beneficial effects of fish oil, rich in omega-3 polyunsaturated fatty acids, and olive oil, rich in monounsaturated fatty acids like oleic acid. ^[145] The protective components found in fish are long chain fatty acids eicosapentaenoic acid (EPA) [Figure 2G] and docosahexaenoic acid (DHA) [Figure 2H] along with proteins, vitamins and minerals. ^[146],[147] On the contrary, there are concerns about potential health hazards due to the environmental contaminants found in fish. ^{[147],[148],[149]} Nevertheless, epidemiological evidence has established that ingestions of fish oils have protective effects on many human disorders including cardiovascular disease and cancer. ^[146] By several mechanisms, omega-3 fatty acids may modify the carcinogenic process, which include suppression of arachidonic acid-derived eicosanoid biosynthesis; influences on transcription factor, gene expression and signal transduction pathways; alteration of estrogen metabolism; effects on free radicals; and involvement in insulin sensitivity and membrane fluidity. ^[150] Furthermore, it has been demonstrated that fish oils have anti-obesity effect and can reduce inflammation. ^{[151],[152],[153],[154]}

Conclusions

References

1.	Shetty P, Schmidhuber J. Introductory lecture the epidemiology and determinants of obesity in developed and developing countries. Int J Vitam Nutr Res 2006;76:157-62.  Back to cited text no. 1
2.	Stoeckli R, Keller U. Nutritional fats and the risk of type 2 diabetes and cancer. Physiol Behav 2004;83:611-5.  Back to cited text no. 2
3.	Hanif MW, Kumar S. Pharmacological management of obesity. Expert Opin Pharmacother 2002;3:1711-8.  Back to cited text no. 3
4.	Calle EE. Obesity and cancer. BMJ 2007;335:1107-8.  Back to cited text no. 4
5.	McTiernan A. Obesity and cancer: The risks, science, and potential management strategies. Oncology (Williston Park) 2005;19:871-81.  Back to cited text no. 5
6.	Ruan H, Lodish HF. Regulation of insulin sensitivity by adipose tissue-derived hormones and inflammatory cytokines. Curr Opin Lipidol 2004;15:297-302.  Back to cited text no. 6
7.	Jee SH, Kim HJ, Lee J. Obesity, insulin resistance and cancer risk. Yonsei Med J 2005;46:449-55.  Back to cited text no. 7
8.	Tilg H, Moschen AR. Adipocytokines: Mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 2006;6:772-83.  Back to cited text no. 8
9.	Cowey S, Hardy RW. The metabolic syndrome: A high-risk state for cancer? Am J Pathol 2006;169:1505-22.  Back to cited text no. 9
10.	Suba Z, Ujpal M. Correlations of insulin resistance and neoplasms. Magy Onkol 2006;50:127-35.  Back to cited text no. 10
11.	Housa D, Housova J, Vernerova Z, Haluzik M. Adipocytokines and cancer. Physiol Res 2006;55:233-44.  Back to cited text no. 11
12.	Kadowaki T, Yamauchi T, Kubota N. The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS. FEBS Lett 2008;582:74-80.   Back to cited text no. 12
13.	Barb D, Pazaitou-Panayiotou K, Mantzoros CS. Adiponectin: A link between obesity and cancer. Expert Opin Investig Drugs 2006;15:917-33.  Back to cited text no. 13
14.	WCRF and AICR. Food, Nutrition and the Prevention of cancer: A global perspective, World Cancer Research Fund and American Institute for Cancer Research, Washington DC: 1997.  Back to cited text no. 14
15.	Wargovich MJ. Nutrition and cancer: The herbal revolution. Curr Opin Clin Nutr Metab Care 1999;2:421-4.  Back to cited text no. 15
16.	Tadjalli-Mehr K, Becker N, Rahu M, Stengrevics A, Kurtinaitis J, Hakama M. Randomized trial with fruits and vegetables in prevention of cancer. Acta Oncol 2003;42:287-93.  Back to cited text no. 16
17.	Block G, Patterson B, Subar A. Fruits, vegetables and cancer prevention: A review of the epidemiologic evidence. Nutr Cancer 1992;18:1-29.  Back to cited text no. 17
18.	Steinmetz KA, Potter JD. Vegetables, fruits and cancer prevention: A review. J Am Diet Assoc 1996;96:1027-39.   Back to cited text no. 18
19.	Friedrich M. Dietary modification of body composition and fat tissue distribution in obese menopausal women. Przegl Lek 2007;64:19-23.   Back to cited text no. 19
20.	Vioque J, Weinbrenner T, Castello A, Asensio L, Garcia de la Hera M. Intake of fruits and vegetables in relation to 10-year weight gain among Spanish adults. Obesity 2008;16:664-70.   Back to cited text no. 20
21.	Nagasako-Akazome Y, Kanda T, Ohtake Y, Shimasaki H, Kobayashi T. Apple polyphenols influence cholesterol metabolism in healthy subjects with relatively high body mass index. J Oleo Sci 2007;56:417-28.   Back to cited text no. 21
22.	Hsu CL, Yen GC. Phenolic compounds: Evidence of inhibitory effects against obesity and their underlying molecular signaling mechanisms. Mol Nutr Food Res 2008;52:53-61.   Back to cited text no. 22
23.	Kang JH, Kim CS, Han IS, Kawada T, Yu R. Capsaicin, a spicy component of hot peppers, modulates adipokine gene expression and protein release from obese-mouse adipose tissue and isolated adipocytes and suppresses the inflammatory responses of adipose tissue macrophages. FEBS Lett 2007;581:4389-96.   Back to cited text no. 23
24.	Sedjo RL, Byers T, Barrera E, Cohen C, Fontham ET, Newman LA, et al . A midpoint assessment of the American Cancer Society challenge goal to decrease cancer incidence by 25% between 1992 and 2015. CA Cancer J Clin 2007;57:326-40.   Back to cited text no. 24
25.	Li H, Stampfer MJ, Giovannucci EL, Morris JS, Willett WC, Gaziano JM, et al . A prospective study of plasma selenium levels and prostate cancer risk. J Natl Cancer Inst 2004;96:696-703.  Back to cited text no. 25
26.	van den Brandt PA, Zeegers MP, Bode P, Goldbohm RA. Toenail selenium levels and the subsequent risk of prostate cancer: A prospective cohort study. Cancer Epidemiol Biomarkers Prev 2003;12:866-71.  Back to cited text no. 26
27.	Brooks JD, Metter EJ, Chan DW, Sokoll LJ, Landis P, Nelson WG, et al . Plasma selenium level before diagnosis and risk of protate cancer development. J Urol 2001;166:2034-8.  Back to cited text no. 27
28.	Helzlsouer KJ, Huang HY, Alberg AJ, Hoffman S, Burke A, Norkus EP, et al . Association and subsequent prostate cancer. J Natl Cancer Inst 2000;92:2018-23.  Back to cited text no. 28
29.	Yoshizawa K, Willett WC, Morris SJ, Stampfer MJ, Spiegelman D, Rimm EB, et al . Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. J Natl Cancer Inst 1998;90:1219-24.  Back to cited text no. 29
30.	Criqui MH, Bangdiwala S, Goodman DS, Blaner WS, Morris JS, Kritchevsky S, et al . Selenium, retinol, retinol-binding protein, and uric acid. Associations with cancer mortality in a population-based prospective case-control study. Ann Epidemiol 1991;1:385-93.  Back to cited text no. 30
31.	Lieberman R, Nelson WG, Sakr WA, Meyskens FL Jr, Klein EA, Wilding G, et al . Executive Summary of the National Cancer Institute Workshop: Highlights and recommendations. Urology 2001;57:4-27.  Back to cited text no. 31
32.	Greenwald P. A favorable view: Progress in cancer prevention and screening. Recent Results Cancer Res 2007;174:3-17.  Back to cited text no. 32
33.	Thorpe JF, Jain S, Marczylo TH, Gescher AJ, Steward WP, Mellon JK. A review of phase III clinical trials of prostate cancer chemoprevention. Ann R Coll Surg Engl 2007;89:207-11.   Back to cited text no. 33
34.	Neill MG, Fleshner NE. An update on chemoprevention strategies in prostate cancer for 2006. Curr Opin Urol 2006;16:132-7.  Back to cited text no. 34
35.	Greenwald P, Lieberman R. Chemoprevention trial for prostate cancer. In: Chung WK, Ilsaacs WB, Simons JW, editors. Prostate cancer: Biology, genetics and new therapeutics. Totowa, NJ: Humana Press; 2000. p. 499-518.  Back to cited text no. 35
36.	Brooks JD, Nelson WG. Chemoprevention trial for prostate cancer. In: Chung WK, Ilsaacs WB, Simons JW, editors. Prostate cancer: Biology, genetics and new therapeutics. Totowa, NJ: Humana Press; 2000. p. 365-75.   Back to cited text no. 36
37.	El-Bayoumy K. The protective role of selenium on genetic damage and on cancer. Mutat Res 2001;475:123-39.  Back to cited text no. 37
38.	Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, et al . Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: A randomised controlled trial. JAMA 1996;276:1957-63.  Back to cited text no. 38
39.	Duffield-Lillico AJ, Reid ME, Turnbull BW, Combs GF Jr, Slate EH, Fischbach LA, et al . Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: A summary report of the Nutritional Prevention of Cancer Trial. Cancer Epidemiol Biomarkers Prev 2002;11:630-9.  Back to cited text no. 39
40.	Marshall JR, Sakr W, Wood D, Berry D, Tangen C, Parker F, et al . Design and progress of a trial of selenium to prevent prostate cancer among men with high-grade prostatic intraepithelial neoplasia. Cancer Epidemiol Biomarkers Prev 2006;15:1479-84.  Back to cited text no. 40
41.	Ansari MS, Gupta NP, Hemal AK. Chemoprevention of carcinoma prostate: A review. Int Urol Nephrol 2002;34:207-14.  Back to cited text no. 41
42.	Tamimi RM, Lagiou P, Adami HO, Trichopoulos D. Prospects for chemoprevention of cancer. J Intern Med 2002;251:286-300.   Back to cited text no. 42
43.	Gandini S, Merzenich H, Robertson C, Boyle P. Meta-analysis of studies on breast cancer risk and diet: The role of fruit and vegetables consumption and intake of associated micronutrients. Eur J Cancer 2000;36:636-46.  Back to cited text no. 43
44.	Haggans CJ, Travelli EJ, Thomas W, Martini MC, Slavin JL. The effect of flaxseed and wheat bran consumption on urinary estrogen metabolities in premenopausal women. Cancer Epidemiol Biomarkers Prev 2000;9:719-25.  Back to cited text no. 44
45.	Sieri S, Krogh V, Pala V, Muti P, Micheli A, Evangelista A, et al . Dietary patterns and risk of breast cancer in the ORDET cohort. Cancer Epidemiol Biomarkers Prev 2004;13:567-72.  Back to cited text no. 45
46.	Prentice RL, Caan B, Chlebowski RT, Patterson R, Kuller LH, Ockene JK, et al . Low-fat dietary pattern and risk of invasive breast cancer: The Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295:629-42.   Back to cited text no. 46
47.	Colditz GA, Frazier AL. Models of breast cancer show that risk is set by events of early life: Prevention efforts must shift focus. Cancer Epidemiol Biomarkers Prev 1995;4:567-71.   Back to cited text no. 47
48.	Goodman MT, Wilkens LR, Hankin JH, Lyu LC, Wu AH, Kolonel LN. Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol 1997;146:294-306.   Back to cited text no. 48
49.	Dalvi TB, Canchola AJ, Horn-Ross PL. Dietary patterns, Mediterranean diet, and endometrial cancer risk. Cancer Causes Control 2007;18:957-66.   Back to cited text no. 49
50.	McCann SE, Freudenheim JL, Marshall JR, Brasure JR, Swanson MK, Graham S. Diet in the epidemiology of endometrial cancer in western New York (United States). Cancer Causes Control 2000;11:965-74.   Back to cited text no. 50
51.	Tao MH, Xu WH, Zheng W, Gao YT, Ruan ZX, Cheng JR, et al . A case-control study in Shanghai of fruit and vegetable intake and endometrial cancer. Br J Cancer 2005;92:2059-64.   Back to cited text no. 51
52.	McCullough ML, Bandera EV, Patel R, Patel AV, Gansler T, Kushi LH, et al . A prospective study of fruits, vegetables, and risk of endometrial cancer. Am J Epidemiol 2007;166:902-11.   Back to cited text no. 52
53.	Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML. Fruits and vegetables and endometrial cancer risk: A systematic literature review and meta-analysis. Nutr Cancer 2007;58:6-21.   Back to cited text no. 53
54.	Horn-Ross PL, John EM, Canchola AJ, Stewart SL, Lee MM. Phytoestrogen intake and endometrial cancer risk. J Natl Cancer Inst 2003;95:1158-64.   Back to cited text no. 54
55.	Littman AJ, Beresford SA, White E. The association of dietary fat and plant foods with endometrial cancer (United States). Cancer Causes Control 2001;12:691-702.   Back to cited text no. 55
56.	Weikert S, Boeing H, Pischon T, Olsen A, Tjonneland A, Overvad K, et al . Fruits and vegetables and renal cell carcinoma: Findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 2006;118:3133-9.   Back to cited text no. 56
57.	Rashidkhani B, Lindblad P, Wolk A. Fruits, vegetables and risk of renal cell carcinoma: A prospective study of Swedish women. Int J Cancer 2005;113:451-5.   Back to cited text no. 57
58.	Hu J, Mao Y, White K. Canadian Cancer Registries Epidemiology Research Group. Diet and vitamin or mineral supplements and risk of renal cell carcinoma in Canada. Cancer Causes Control 2003;14:705-14.   Back to cited text no. 58
59.	Galeone C, Pelucchi C, Talamini R, Negri E, Montella M, Ramazzotti V, et al . Fibre intake and renal cell carcinoma: A case-control study from Italy. Int J Cancer 2007;121:1869-72.   Back to cited text no. 59
60.	Gonzalez CA, Pera G, Agudo A, Bueno-de-Mesquita HB, Ceroti M, Boeing H, et al . Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Int J Cancer 2006;118:2559-66.   Back to cited text no. 60
61.	Freedman ND, Park Y, Subar AF, Hollenbeck AR, Leitzmann MF, Schatzkin A, et al . Fruit and vegetable intake and esophageal cancer in a large prospective cohort study. Int J Cancer 2007;121:2753-60.   Back to cited text no. 61
62.	Terry P, Lagergren J, Hansen H, Wolk A, Nyren O. Fruit and vegetable consumption in the prevention of oesophageal and cardia cancers. Eur J Cancer Prev 2001;10:365-9.   Back to cited text no. 62
63.	Jarvinen R, Knekt P, Hakulinen T, Rissanen H, Heliovaara M. Dietary fat, cholesterol and colorectal cancer in a prospective study. Br J Cancer 2001;85:357-61.   Back to cited text no. 63
64.	Mathew A, Sinha R, Burt R, Caan B, Paskett E, Iber F, et al . Meat intake and the recurrence of colorectal adenomas. Eur J Cancer Prev 2004;13:159-64.   Back to cited text no. 64
65.	Mathew A, Peters U, Chatterjee N, Kulldorff M, Sinha R. Fat, fiber, fruits, vegetables, and risk of colorectal adenomas. Int J Cancer 2004;108:287-92.   Back to cited text no. 65
66.	Michels KB, Giovannucci E, Chan AT, Singhania R, Fuchs CS, Willett WC. Fruit and vegetable consumption and colorectal adenomas in the Nurses' Health Study. Cancer Res 2006;66:3942-53.   Back to cited text no. 66
67.	Lin J, Zhang SM, Cook NR, Rexrode KM, Liu S, Manson JE, et al . Dietary intakes of fruit, vegetables, and fiber, and risk of colorectal cancer in a prospective cohort of women (United States). Cancer Causes Control 2005;16:225-33.   Back to cited text no. 67
68.	Baron JA, Beach M, Mandel JS, van Stolk RU, Haile RW, Sandler RS, et al . Calcium supplements for the prevention of colorectal adenomas. N Engl J Med 1999;340:101-7.   Back to cited text no. 68
69.	Giovannucci E, Stampfer MJ, Colditz GA, Hunter DJ, Fuchs C, Rosner BA, et al . Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med 1998;129:517-24.   Back to cited text no. 69
70.	Cook NR, Lee IM, Gaziano JM, Gordon D, Ridker PM, Manson JE, et al . Low-dose aspirin in the primary prevention of cancer: The Women's Health Study: A randomized controlled trial. JAMA 2005;294:47-55.   Back to cited text no. 70
71.	Dube C, Rostom A, Lewin G, Tsertsvadze A, Barrowman N, Code C, et al . The use of aspirin for primary prevention of colorectal cancer: A systematic review prepared for the US Preventive Services Task Force. Ann Intern Med 2007;146:365-75.   Back to cited text no. 71
72.	Lanzotti V. The analysis of onion and garlic. J Chromatogr A 2006;1112:3-22.  Back to cited text no. 72
73.	Fleischauer AT, Arab L. Garlic and cancer: A critical review of the epidemiologic literature. J Nutr 2001;131:1032S-40S.  Back to cited text no. 73
74.	Hsing AW, Chokkalingam AP, Gao YT, Madigan MP, Deng J, Gridley G, et al . Allium vegetables and risk of prostate cancer: A population-based study. J Natl Cancer Inst 2002;94:1648-51.  Back to cited text no. 74
75.	Setiawan VW, Yu GP, Lu QY, Lu ML, Yu SZ, Mu L, et al . Allium vegetables and stomach cancer risk in China. Asian Pac J Cancer Prev 2005;6:387-95.  Back to cited text no. 75
76.	Galeone C, Pelucchi C, Levi F, Negri E, Franceschi S, Talamini R, et al . Onion and garlic use and human cancer. Am J Clin Nutr 2006;84:1027-32.  Back to cited text no. 76
77.	Shukla Y, Kalra N. Cancer chemoprevention with garlic and its constituents. Cancer Lett 2007;247:167-81.  Back to cited text no. 77
78.	Jakubikova J, Sedlak J. Garlic-derived organosulfides induce cytotoxicity, apoptosis, cell cycle arrest and oxidative stress in human colon carcinoma cell lines. Neoplasma 2006;53:191-9.  Back to cited text no. 78
79.	Herman-Antosiewicz A, Powolny AA, Singh SV. Molecular targets of cancer chemoprevention by garlic-derived organosulfides. Acta Pharmacol Sin 2007;28:1355-64.  Back to cited text no. 79
80.	El-Bayoumy K, Sinha R, Pinto JT, Rivlin RS. Cancer chemoprevention by garlic and garlic-containing sulfur and selenium compounds. J Nutr 2006;136:864S-9S.  Back to cited text no. 80
81.	Raghuram TC, Pasricha S, Sharma RD. Diet and diabetes. New Delhi: Indian Council of Medical Research; 2000. p. 19-22.  Back to cited text no. 81
82.	Chevallier A. Encyclopedia of herbal medicine. New York: Dorling Kindersley; 2000. p. 271.  Back to cited text no. 82
83.	Raju J, Patlolla JM, Swamy MV, Rao CV. Diosgenin, a steroid saponin of Trigonella foenum graecum (Fenugreek), inhibits azoxymethane-induced aberrant crypt foci formation in F344 rats and induces apoptosis in HT-29 human colon cancer cells. Cancer Epidemiol Biomarkers Prev 2004;13:1392-8.   Back to cited text no. 83
84.	Sur P, Das M, Gomes A, Vedasiromoni JR, Sahu NP, Banerjee S, et al . Trigonella foenum graecum (fenugreek) seed extract as an antineoplastic agent. Phytother Res 2001;15:257-9.  Back to cited text no. 84
85.	Devasena T, Venugopal Menon P. Fenugreek seeds modulate 1,2-dimethylhydrazine-induced hepatic oxidative stress during colon carcinogenesis. Ital J Biochem 2007;56:28-34.  Back to cited text no. 85
86.	Murakami T, Kishi A, Matsuda H, Yoshikawa M. Medicinal food stuffs, XVII: Fenugreek seed, (3): Structures of new furostanol-type steroid saponins, trigoneosides Xa, Xb, XIb, XIIa, XIIb, and XIIIa, from the seeds of Egyptian Trigonella foenum-graecum L. Chem Pharm Bull 2000;48:994-1000.  Back to cited text no. 86
87.	Corbiere C, Liagre B, Terro F, Beneytout JL. Induction of antiproliferative effect by diosgenin through activation of p53, release of apoptosis-inducing factor (AIF) and modulation of caspase-3 activity in different human cancer cells. Cell Res 2004;14:188-96.  Back to cited text no. 87
88.	Liu MJ, Wang Z, Ju Y, Wong RN, Wu QY. Diosgenin induces cell cycle arrest and apoptosis in human leukemia K562 cells with the disruption of Ca 2+ homeostasis. Cancer Chemother Pharmacol 2005;55:79-90.  Back to cited text no. 88
89.	Li J, Liu X, Guo M, Liu Y, Liu S, Yao S. Electrochemical study of breast cancer cells MCF-7 and its application in evaluating the effect of diosgenin. Anal Sci 2005;21:561-4.  Back to cited text no. 89
90.	Raju J, Bird RP. Diosgenin, a naturally occurring furostanol saponin suppresses 3-hydroxy-3-methylglutaryl CoA reductase expression and induces apoptosis in HCT-116 human colon carcinoma cells. Cancer Lett 2007;255:194-204.  Back to cited text no. 90
91.	Wang LJ, Wang Y, Chen SW, Ma JS, Fu Q, Wang BX. The antitumor activity of diosgenin in vivo and in vitro . Zhongguo Zhong Yao Za Zhi 2002;27:777-9.  Back to cited text no. 91
92.	Bushman JL. Green tea and cancer in humans: A review of the literature. Nutr Cancer 1998;31:151-9.   Back to cited text no. 92
93.	Mukhtar H, Ahmad N. Mechanism of cancer chemopreventive activity of green tea. Proc Soc Exp Biol Med 1999;220:234-8.  Back to cited text no. 93
94.	Ray A. Cancer preventive role of selected dietary factors. Indian J Cancer 2005;42:15-24.  Back to cited text no. 94  [PUBMED]
95.	Ju J, Lu G, Lambert JD, Yang CS. Inhibition of carcinogenesis by tea constituents. Semin Cancer Biol 2007;17:395-402.  Back to cited text no. 95
96.	Moon HS, Lee HG, Choi YJ, Kim TG, Cho CS. Proposed mechanisms of (-)-epigallocatechin-3-gallate for anti-obesity. Chem Biol Interact 2007;167:85-98.  Back to cited text no. 96
97.	Wolfram S. Effects of green tea and EGCG on cardiovascular and metabolic health. J Am Coll Nutr 2007;26:373S-88S.  Back to cited text no. 97
98.	Garcia MC, Torre M, Marina ML, Laborda F. Composition and characterization of soyabean and related products. Crit Rev Food Sci Nutr 1997;37:361-91.  Back to cited text no. 98
99.	Velasquez MT, Bhathena SJ. Role of dietary soy protein in obesity. Int J Med Sci 2007;4:72-82.  Back to cited text no. 99
100.	Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer 2006;55:1-12.  Back to cited text no. 100
101.	Erdman JW Jr, Badger TM, Lampe JW, Setchell KD, Messina M. Not all soy products are created equal: Caution needed in interpretation of research results. J Nutr 2004;134:1229S-33S.   Back to cited text no. 101
102.	Zhang HM, Chen SW, Zhang LS, Feng XF. Effects of soy isoflavone on low-grade inflammation in obese rats. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2006;31:336-9.  Back to cited text no. 102
103.	Ali AA, Velasquez MT, Hansen CT, Mohamed AI, Bhathena SJ. Effects of soybean isoflavones, probiotics and their interactions on lipid metabolism and endocrine system in an animal model of obesity and diabetes. J Nutr Biochem 2004;15:583-90.  Back to cited text no. 103
104.	Deibert P, Konig D, Schmidt-Trucksaess A, Zaenker KS, Frey I, Landmann U, et al . Weight loss without losing muscle mass in pre-obese and obese subjects induced by a high-soy-protein diet. Int J Obes Relat Metab Disord 2004;28:1349-52.  Back to cited text no. 104
105.	Nagasawa A, Fukui K, Funahashi T, Maeda N, Shimomura I, Kihara S, et al . Effects of soy protein diet on the expression of adipose genes and plasma adiponectin. Horm Metab Res 2002;34:635-9.  Back to cited text no. 105
106.	Qin LQ, Xu JY, Wang PY, Hoshi K. Soy food intake in the prevention of breast cancer risk in women: A meta-analysis of observational epidemiological studies. J Nutr Sci Vitaminol (Tokyo) 2006;52:428-36.  Back to cited text no. 106
107.	Do MH, Lee SS, Jung PJ, Lee MH. Intake of fruits, vegetables, and soy foods in relation to breast cancer risk in Korean women: A case-control study. Nutr Cancer 2007;57:20-7.  Back to cited text no. 107
108.	Kurahashi N, Iwasaki M, Sasazuki S, Otani T, Inoue M, Tsugane S, et al . Soy product and isoflavone consumption in relation to prostate cancer in Japanese men. Cancer Epidemiol Biomarkers Prev 2007;16:538-45.   Back to cited text no. 108
109.	Nagata Y, Sonoda T, Mori M, Miyanaga N, Okumura K, Goto K, et al . Dietary isoflavones may protect against prostate cancer in Japanese men. J Nutr 2007;137:1974-9.  Back to cited text no. 109
110.	Oba S, Nagata C, Shimizu N, Shimizu H, Kametani M, Takeyama N, et al . Soy product consumption and the risk of colon cancer: A prospective study in Takayama, Japan. Nutr Cancer 2007;57:151-7.  Back to cited text no. 110
111.	Mukhopadhyay S, Ballard BR, Mukherjee S, Kabir SM, Das SK. Beneficial effects of soy protein in the initiation and progression against dimethylbenz[a]anthracene-induced breast tumors in female rats. Mol Cell Biochem 2006;290:169-76.  Back to cited text no. 111
112.	Farina HG, Pomies M, Alonso DF, Gomez DE. Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer. Oncol Rep 2006;16:885-91.  Back to cited text no. 112
113.	Gossner G, Choi M, Tan L, Fogoros S, Griffith KA, Kuenker M, et al . Genistein-induced apoptosis and autophagocytosis in ovarian cancer cells. Gynecol Oncol 2007;105:23-30.  Back to cited text no. 113
114.	Rice L, Handayani R, Cui Y, Medrano T, Samedi V, Baker H, et al . Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells. J Nutr 2007;137:964-72.  Back to cited text no. 114
115.	McCarty MF. Does bitter melon contain an activator of AMP-activated kinase? Med Hypotheses 2004;63:340-3.  Back to cited text no. 115
116.	Huang HL, Hong YW, Wong YH, Chen YN, Chyuan JH, Huang CJ, et al . Bitter melon (Momordica charantia L.) inhibits adipocyte hypertrophy and down regulates lipogenic gene expression in adipose tissue of diet-induced obese rats. Br J Nutr 2008;99:230-9.  Back to cited text no. 116
117.	Chen Q, Li ET. Reduced adiposity in bitter melon (Momordica charantia) fed rats is associated with lower tissue triglyceride and higher plasma catecholamines. Br J Nutr 2005;93:747-54.  Back to cited text no. 117
118.	Chan LL, Chen Q, Go AG, Lam EK, Li ET. Reduced adipocity in bitter melon (Momordica charantia)-fed rats is associated with increased lipid oxidative enzyme activities and uncoupling protein expression. J Nutr 2005;135:2517-23.  Back to cited text no. 118
119.	Fernandes NP, Lagishetty CV, Panda VS, Naik SR. An experimental evaluation of the antidiabetic and antilipidemic properties of a standardized Momordica charantia fruit extract. BMC Complement Altern Med 2007;7:29-36.  Back to cited text no. 119
120.	Sridhar MG, Vinayagamoorthi R, Arul Suyambunathan V, Bobby Z, Selvaraj N. Bitter gourd (Momordica charantia) improves insulin sensitivity by increasing skeletal muscle insulin-stimulated IRS-1 tyrosine phosphorylation in high-fat-fed rats. Br J Nutr 2008;99:806-12.   Back to cited text no. 120
121.	Yasui Y, Hosokawa M, Sahara T, Suzuki R, Ohgiya S, Kohno H, et al . Bitter gourd seed fatty acid rich in 9c,11t,13t-conjugated linolenic acid induces apoptosis and up-regulates the GADD45, p53 and PPAR gamma in human colon cancer Caco-2 cells. Prostaglandins Leukot Essent Fatty Acids 2005;73:113-9.  Back to cited text no. 121
122.	Khan SA. Bitter gourd (Momordica charantia): A potential mechanism in anti-carcinogenesis of colon. World J Gastroenterol 2007;13:1761-2.   Back to cited text no. 122
123.	Lee-Huang S, Huang PL, Sun Y, Chen HC, Kung HF, Huang PL, et al . Inhibition of MDA-MB-231 human breast tumor xenografts and HER2 expression by anti-tumor agents GAP31 and MAP30. Anticancer Res 2000;20:653-9.  Back to cited text no. 123
124.	Ganguly C, De S, Das S. Prevention of carcinogen-induced mouse skin papilloma by whole fruit aqueous extract of Momordica charantia. Eur J Cancer Prev 2000;9:283-8.  Back to cited text no. 124
125.	Nagasawa H, Watanabe K, Inatomi H. Effects of bitter melon (Momordica charantia l.) or ginger rhizome (Zingiber offifinale rocs) on spontaneous mammary tumorigenesis in SHN mice. Am J Chin Med 2002;30:195-205.  Back to cited text no. 125
126.	Chiampanichayakul S, Kataoka K, Arimochi H, Thumvijit S, Kuwahara T, Nakayama H, et al . Inhibitory effects of bitter melon (Momordica charantia Linn.) on bacterial mutagenesis and aberrant crypt focus formation in the rat colon. J Med Invest 2001;48:88-96.  Back to cited text no. 126
127.	Delmas D, Lancon A, Colin D, Jannin B, Latruffe N. Resveratrol as a chemopreventive agent:a promising molecule for fighting cancer. Curr Drug Targets 2006;7:423-42.   Back to cited text no. 127
128.	Benitez DA, Pozo-Guisado E, Alvarez-Barrientos A, Fernandez-Salguero PM, Castellon EA. Mechanisms involved in resveratrol-induced apoptosis and cell cycle arrest in prostate cancer-derived cell lines. J Androl 2007;28:282-93.  Back to cited text no. 128
129.	Tang HY, Shih A, Cao HJ, Davis FB, Davis PJ, Lin HY. Resveratrol induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cells. Mol Cancer Ther 2006;5:2034-42.  Back to cited text no. 129
130.	Rimando AM, Cuendet M, Desmarchelier C, Mehta RG, Pezzuto JM, Duke SO. Cancer chemopreventive and antioxidant activities of pterostilbene: A naturally occurring analogue of resveratrol. J Agric Food Chem 2002;50:3453-7.  Back to cited text no. 130
131.	Waffo-Teguo P, Hawthorne ME, Cuendet M, Merillon JM, Kinghorn AD, Pezzuto JM, et al . Potential cancer-chemopreventive activities of wine stilbenoids and flavans extracted from grape (Vitis vinifera) cell cultures. Nutr Cancer 2001;40:173-9.  Back to cited text no. 131
132.	Wolter F, Clausnitzer A, Akoglu B, Stein J. Piceatannol, a natural analog of resveratrol, inhibits progression through the S phase of the cell cycle in colorectal cancer cell lines. J Nutr 2002;132:298-302.  Back to cited text no. 132
133.	Shibata MA, Akao Y, Shibata E, Nozawa Y, Ito T, Mishima S, et al . Vaticanol C, a novel resveratrol tetramer, reduces lymph node and lung metastasis of mouse mammary carcinoma carrying p53 mutation. Cancer Chemother Pharmacol 2007;60:681-91.  Back to cited text no. 133
134.	Shankar S, Singh G, Srivastava RK. Chemoprevention by resveratrol: Molecular mechanisms and therapeutic potential. Front Biosci 2007;12:4839-54.  Back to cited text no. 134
135.	Rimando AM, Nagmani R, Feller DR, Yokoyama W. Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters. J Agric Food Chem 2005;53:3403-7.  Back to cited text no. 135
136.	Qiao L, Shao J. SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-binding protein α transcriptional complex. J Biol Chem 2006;281:39915-24.  Back to cited text no. 136
137.	Qiang L, Wang H, Farmer SR. Adiponectin secretion is regulated by SIRT1 and the endoplasmic reticulum oxidoreductase Ero1-Lα. Mol Cell Biol 2007;27:4698-707.  Back to cited text no. 137
138.	Subauste AR, Burant CF. Role of FoxO1 in FFA-induced oxidative stress in adipocytes. Am J Physiol Endocrinol Metab 2007;293:E159-64.  Back to cited text no. 138
139.	Van Loon LC, Van Strien EA. The families of pathogenesis-related proteins, their activities, and comparative analysis of PR-1 types proteins. Physiol Mol Plant Pathol 1999;55:85-97.  Back to cited text no. 139
140.	Monteiro S, Barakat M, Picarra-Pereira MA, Teixeira AR, Ferreira RB. Osmotin and thaumatin from grape: A putative general defense mechanism against pathogenic fungi. Phytopathology 2003;93:1505-12.  Back to cited text no. 140
141.	Breiteneder H. Thaumatin-like proteins: A new family of pollen and fruit allergens. Allergy 2004;59:479-81.  Back to cited text no. 141
142.	Kant R. Sweet proteins: Potential replacement for artificial low calorie sweeteners. Nutr J 2005;4:5-10.  Back to cited text no. 142
143.	Narasimhan ML, Coca MA, Jin J, Yamauchi T, Ito Y, Kadowaki T, et al . Osmotin is a homolog of mammalian adiponectin and controls apoptosis in yeast through a homolog of mammalian adiponectin receptor. Mol Cell 2005;17:171-80.  Back to cited text no. 143
144.	Kelesidis I, Kelesidis T, Mantzoros CS. Adiponectin and cancer: A systematic review. Br J Cancer 2006;94:1221-5.   Back to cited text no. 144
145.	Granados S, Quiles JL, Gil A, Ramirez-Tortosa MC. Dietary lipids and cancer. Nutr Hosp 2006;21:42-54.  Back to cited text no. 145
146.	Siddiqui RA, Shaikh SR, Sech LA, Yount HR, Stillwell W, Zaloga GP. Omega 3-fatty acids: Health benefits and cellular mechanisms of action. Mini Rev Med Chem 2004;4:859-71.  Back to cited text no. 146
147.	Domingo JL. Omega-3 fatty acids and the benefits of fish consumption: Is all that glitters gold? Environ Int 2007;33:993-8.  Back to cited text no. 147
148.	Judd N, Griffith WC, Faustman EM. Contribution of PCB exposure from fish consumption to total dioxin-like dietary exposure. Regul Toxicol Pharmacol 2004;40:125-35.  Back to cited text no. 148
149.	Foran JA, Carpenter DO, Hamilton MC, Knuth BA, Schwager SJ. Risk-based consumption advice for farmed Atlantic and wild Pacific salmon contaminated with dioxins and dioxin-like compounds. Environ Health Perspect 2005;113:552-6.  Back to cited text no. 149
150.	Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A. Dietary long-chain n-3 fatty acids for the prevention of cancer: A review of potential mechanisms. Am J Clin Nutr 2004;79:935-45.  Back to cited text no. 150
151.	Mori T, Kondo H, Hase T, Tokimitsu I, Murase T. Dietary fish oil upregulates intestinal lipid metabolism and reduces body weight gain in C57BL/6J mice. J Nutr 2007;137:2629-34.  Back to cited text no. 151
152.	Parra D, Bandarra NM, Kiely M, Thorsdottir I, Martinez JA. Impact of fish intake on oxidative stress when included into a moderate energy-restricted program to treat obesity. Eur J Nutr 2007;46:460-7.  Back to cited text no. 152
153.	Babcock TA, Dekoj T, Espat NJ. Experimental studies defining omega-3 fatty acid antiinflammatory mechanisms and abrogation of tumor-related syndromes. Nutr Clin Pract 2005;20:62-74.  Back to cited text no. 153
154.	La Guardia M, Giammanco S, Di Majo D, Tabacchi G, Tripoli E, Giammanco M. Omega 3 fatty acids: Biological activity and effects on human health. Panminerva Med 2005;47:245-57.  Back to cited text no. 154

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