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REVIEW ARTICLE
Year : 2009  |  Volume : 55  |  Issue : 1  |  Page : 45-54

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


1 National Cancer Registry Programme (ICMR), New BEL Road, Bangalore, India
2 Department of Bio-medical Sciences, Meharry Medical College, Nashville, TN 37208, USA
3 Department of Biochemistry and Molecular Biology, Atlantic Research Center, Dalhousie University, Halifax, Nova Scotia, Canada
4 Hormel Institute, University of Minnesota, Austin, MN 55912, USA

Date of Submission26-Apr-2008
Date of Decision30-May-2008
Date of Acceptance30-Jul-2008
Date of Web Publication24-Feb-2009

Correspondence Address:
A Ray
Hormel Institute, University of Minnesota, Austin, MN 55912
USA
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DOI: 10.4103/0022-3859.43549

PMID: 19242081

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 :: Abstract 

Obesity is a growing health problem in developed nations and in countries that are in the process of westernization like India. Obesity is linked with several health disorders such as hypertension and cardiovascular diseases, Type 2 diabetes, dyslipidemia and certain cancers. Currently, obesity-related malignancies, e.g., cancers of the breast, prostate and colon are the leading cancers in the industrialized societies. An increased amount of fat or adipose tissue in an overweight or obese person probably influences the development of cancer by releasing several hormone-like factors or adipokines. The majority of adipokines are pro-inflammatory, which promote pathological conditions like insulin resistance and cancer. On the other hand, many recent studies have shown that adiponectin, an anti-inflammatory adipokine, has anti-cancer and insulin-sensitizing effects. Adiponectin exerts its physiological functions chiefly by activation of AMP kinase via adiponectin receptors. Interestingly, several fruits and vegetables may contain adiponectin-like molecules or may increase the biosynthesis of adiponectin in our body. Studies on adiponectin analogues or adiponectin receptor agonists are a promising area of cancer chemoprevention research. In general, fruits and vegetables contain various dietary substances such as vitamins, minerals (like calcium and selenium), fiber and phytochemicals or phenolic compounds (like flavonoids and vanilloids), which may act as anti-cancer agents. Similarly, several dietary constituents including phytochemicals may have anti-obesity effects. Consumption of such dietary compounds along with caloric restriction and physical activity may be helpful in preventing obesity-related cancers. For this review article, we searched PubMed primarily to get the relevant literature.


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


How to cite this article:
Murthy N S, Mukherjee S, Ray G, Ray A. Dietary factors and cancer chemoprevention: An overview of obesity-related malignancies. J Postgrad Med 2009;55:45-54

How to cite this URL:
Murthy N S, Mukherjee S, Ray G, Ray A. Dietary factors and cancer chemoprevention: An overview of obesity-related malignancies. J Postgrad Med [serial online] 2009 [cited 2014 Jul 25];55:45-54. Available from: http://www.jpgmonline.com/text.asp?2009/55/1/45/43549


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 Top


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 Top


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 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). [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) 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) 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, piceatannol 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) and docosahexaenoic acid (DHA) 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 Top


In relation to industrialization and westernized lifestyle, the prevalence of obesity has been increasing throughout the world. Interestingly, insulin resistance is the common feature of all obesity-related health problems including cardiovascular diseases, diabetes and cancer. Although, it is certain that insulin resistance is a state of low-grade inflammation, several lacunae exist about the concept of this disorder. A precise knowledge will lead to better measurements of insulin resistance, a clear idea of the related situations like metabolic syndrome and leptin resistance, and a proper understanding concerning hormonal aspects such as nature of estrogen metabolism in breast and endometrial cancers. Amazingly, a growing body of published data indicates a promising role of phytochemicals/polyphenols both in obesity and cancer. Apart from antioxidant and anti-inflammatory properties, many of the phytochemicals may exert insulin-sensitizing effect by either increasing the levels of adiponectin or improving adiponectin signaling. On the other hand, reports also have revealed that some plant phenolic compounds may exhibit pro-oxidant activity. Therefore, considering the negative aspects of plant products including mycotoxins and pesticide residues, consumptions of properly preserved and clean fruits and vegetables containing various types of phytochemicals/phenolic compounds along with maintenance of appropriate energy balance by regular physical activity and caloric restriction are probably helpful. However, a clear understanding of the molecular mechanisms of the development of obesity and its interactions with the dietary factors are crucial to formulate an effective preventive strategy against obesity-related diseases including cancer.

 
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