Dietary fibre and colon cancer: epidemiologic and experimental evidence.

Epidemiologic studies have identified two dietary factors, a relatively high intake of fat and a relatively low intake of fibre, that are associated with colon cancer in humans. However, a recent study has shown a low risk of large bowel cancer in a rural Finnish population with a high dietary intake of fat, but also a high intake of fibre. Observations in humans and studies in animals have indicated that dietary fibre may protect against colon carcinogenesis by binding bile acids in the intestinal tract, by a direct effect on the colonic mucosa and by an indirect effect on the metabolism of carcinogens. The strength of protection varies with the type of fibre.     

Protein kinase C betaII and TGFbetaRII in omega-3 fatty acid-mediated inhibition of colon carcinogenesis

Increasing evidence demonstrates that protein kinase C betaII (PKCbetaII) promotes colon carcinogenesis. We previously reported that colonic PKCbetaII is induced during colon carcinogenesis in rodents and humans, and that elevated expression of PKCbetaII in the colon of transgenic mice enhances colon carcinogenesis. Here, we demonstrate that PKCbetaII represses transforming growth factor beta receptor type II (TGFbetaRII) expression and reduces sensitivity to TGF-beta-mediated growth inhibition in intestinal epithelial cells. Transgenic PKCbetaII mice exhibit hyperproliferation, enhanced colon carcinogenesis, and marked repression of TGFbetaRII expression. Chemopreventive dietary omega-3 fatty acids inhibit colonic PKCbetaII activity in vivo and block PKCbetaII-mediated hyperproliferation, enhanced carcinogenesis, and repression of TGFbetaRII expression in the colonic epithelium of transgenic PKCbetaII mice. These data indicate that dietary omega-3 fatty acids prevent colon cancer, at least in part, through inhibition of colonic PKCbetaII signaling and restoration of TGF-beta responsiveness.     

Dietary fiber decreases colonic epithelial cell proliferation and protein synthetic rates in human subjects

Although it has been proposed that high fiber consumption can prevent proliferative diseases of the colon, the clinical data to support this hypothesis have been inconsistent. To provide a more robust measure of the effects of fiber on colonic mucosal growth than previous studies, we evaluated both cell proliferation and colonic mucosal protein synthesis in nine healthy volunteers after they consumed a typical Western diet (<20 g fiber/day) or a Western diet supplemented with wheat bran (24 g/day) in a randomized crossover design. Biopsies taken from the sigmoid colon were used to assess mucosal proliferation by determining proliferating cell nuclear antigen (PCNA) in crypt cells and to assess mucosal protein synthetic rate using stable isotopically labeled leucine infusion. Fiber supplementation produced a 12% decrease in labeling index (%crypt cells stained with PCNA) (P < 0.001) and an 11% decrease in mucosal protein fractional synthetic rate (FSR; P < 0.05). Moreover, mucosal protein FSR correlated directly with labeling index (r2= 0.22, P < 0.05). These data demonstrate that increased wheat bran consumption decreases colonic mucosal proliferation and support the potential importance of dietary fiber in preventing proliferative diseases of the colon.     

Ascorbate, cyclic nucleotides, citrus and a model for preventing large bowel cancer

There is evidence that the risk for developing large bowel cancer is dependent on dietary practice. The “western” diet, high in meats, proteins, fats and refined carbohydrates, and low in fiber, has been causally related to this disease. Diet is known to affect microflora, bile acids, neutral sterols and bacterial enzyme activities in the bowel. These changes may result in the production of carcinogens/ cocarcinogens within the large bowel (in situ). Current evidence suggests that nitrosamines and secondary bile acids and/or cholesterol metabolites may be the carcinogens and cocarcinogens respectively. Although the population of the United States is considered at high risk for developing large bowel cancer, the South-East as well as southern California, Arizona and Florida residents are interesting exceptions. The incidence of large bowel cancer is two-fold lower in these regions, in spite of many residents having previously lived in the higher risk north-eastern and mid-western states. Preliminary studies of dietary practices (meat consumption and dietary fiber) did not find differences which would account for the low risk regions. Our hypothesis is that citrus fruit consumption is the prime factor which can account for these low risk regions. Consumption of citrus fruits may prevent in situ production of fecal nitrosamines, secondary bile acids, and cholesterol metabolites. It has also been reported that ascorbate induces regression of preneoplastic bowel polyps. We suggest that polyp regression is the result of a cellular response in which ascorbate increases cyclic adenosine monophosphate, and the result is biochemical differentiation with an enhanced extrusion of aberrant polyp cells. Florida, which has a large immigrating population from the high risk north-eastern United States, provides an excellent model for metabolic-epidemiological studies of an area at low risk for colon cancer.     

Carcinogens in the diet vs. overnutrition. Individual dietary habits, malnutrition, and genetic susceptibility modify carcinogenic potency and cancer risk.

Chemical carcinogens in the diet cannot explain the cancer incidence attributed by epidemiologists to dietary factors when the calculation is based on average exposure levels and conservative estimates of carcinogenic potencies. In a previous review, the discrepancy was explained primarily by overnutrition to which a carcinogenic potency was assigned from dietary restriction experiments and the associated reduction in spontaneous tumor incidence (W.K. Lutz and J. Schlatter, Chemical carcinogens and overnutrition in diet-related cancer, Carcinogenesis 13 [1992] 2211-2216). Here, additional aspects are introduced. They focus on using individual rather than averaged data, both for exposure and susceptibility. First, under conditions of a sublinear (convex) dose-response, the cancer incidence obtained by using an average exposure level is lower than if individual exposure levels associated with particular dietary habits are taken into account. Second, carcinogenic factors, including those unrelated to the diet (e.g., smoking), can act synergistically. Third, the potency of dietary carcinogens is increased under conditions of malnutrition in the sense of a deficiency of protective factors, such as those available with fruits, vegetables, and fibers. Quantitatively, this aspect may be particularly important because it simultaneously increases the efficacy of a multitude of carcinogens. It is concluded that chemical carcinogens could be as important as overnutrition for diet-related cancer.     

Relation between colonic proglucagon expression and metabolic response to oligofructose in high fat diet-fed mice

Several data suggest that fermentable dietary fiber could play a role in the control of obesity and associated metabolic disorders. The aim of this study was to investigate the putative role of short chain fructo-oligosaccharide (OFS) - a non-digestible oligosaccharide - in mice fed a standard diet and in mice fed two distinct high fat diets inducing metabolic disorders associated to obesity. We confirmed, in mice, several effects previously shown in rats fed a standard diet enriched with OFS, namely an increase in total and empty caecum weight, a significant decrease in epididymal fat mass, and an increase in colonic and portal plasma glucagon-like peptide-1 (GLP-1), a phenomenon positively correlated with a higher colonic proglucagon mRNA level. Curiously, 4-week treatment with OFS added at the same dose induced different effects when added in the two different high fat diets. OFS decreased energy intake, body weight gain, glycemia, and epididymal fat mass only when added together with the high fat-carbohydrate free diet, in which OFS promoted colonic proglucagon expression and insulin secretion. Our results support an association between the increase in proglucagon expression in the proximal colon and OFS effects on glycemia, fat mass development, and/or body weight gain. In conclusion, dietary oligosaccharides would constitute an interesting class of dietary fibers promoting, in certain conditions, endogenous GLP-1 production, with beneficial physiological consequences. This remains to be proven in human studies.     

Update on the effects of vitamins A, C, and E and selenium on carcinogenesis

The effects of vitamins A, C, and E and of selenium on carcinogenesis are briefly summarized and updated. These vitamins and minerals were selected because they have been studied extensively in recent years with a variety of carcinogenesis models. The consumption of vitamin A and its precursors (carotenoids) has been negatively correlated with cancer at a number of sites, particularly the lung. Animal investigations on vitamin A involvement in carcinogenesis have generally been of three types: those assessing the effect of vitamin A deficiency, the effect of excess vitamin A, or the effect of supplementation with synthetic analogs of vitamin A. Vitamin A deficiency had no effect on salivary gland carcinogenesis, enhanced urinary bladder, lung, and liver carcinogenesis, and inhibited colon carcinogenesis. Excess of various forms of vitamin A enhanced or inhibited skin tumorigenesis, inhibited mammary carcinogenesis in rats (but not in mice), and carcinogenesis of the forestomach, liver, and urinary bladder (with one model, but not with another), or enhanced or did not influence lung carcinogenesis. Vitamin A analogs have enhanced or inhibited skin tumorigenesis, inhibited salivary gland, mammary, and urinary bladder carcinogenesis, enhanced tracheal and liver carcinogenesis, and either enhanced or inhibited pancreas carcinogenesis, depending upon the model employed. Although retinoids have been shown to inhibit carcinogenesis at many sites, numerous negative studies have been reported and some reports have indicated enhanced carcinogenesis. The most convincing evidence for the involvement of vitamin C in cancer prevention is the ability of ascorbic acid to prevent formation of nitrosamine and of other N-nitroso compounds. In addition vitamin C supplementation was shown to inhibit skin, nose, tracheal, lung, and kidney carcinogenesis, to either not influence or enhance skin, mammary gland, and colon carcinogenesis, and to enhance urinary bladder carcinogenesis, when given as sodium ascorbate, but not when given as ascorbic acid. Like vitamin C, vitamin E can inhibit nitrosation. Vitamin E was shown to inhibit skin, cheek pouch, and forestomach carcinogenesis, to enhance or inhibit colon carcinogenesis, and to have no effect on or to inhibit mammary gland carcinogenesis, depending upon the method of vitamin E administration or the level of dietary selenium or dietary fat. Selenium effects on carcinogenesis have been recently reviewed and the present discussion only updates this area by indicating that enhancement of carcinogenesis by dietary selenium supplements has been observed in the liver, pancreas, and skin.(ABSTRACT TRUNCATED AT 400 WORDS)     

Alteration of Bile Salt Metabolism by Dietary Fibre (Bran)

Feeding dietary fibre in the form of bran induced changes in bile salt metabolism in five people with intact gall bladders. There was evidence of reduced dehydroxylation of bile salts; the proportion of deoxycholate conjugates in bile was reduced and the transfer of radioactivity from labelled taurocholate to deoxycholate was decreased. These findings, which were independent of changes in intestinal transit rate, imply that bran reduced the degradation of bile salts by colonic bacteria. This property of bran accords with recent theories that fibre-depleted diets favour the degradation of bile salts in the colon. These findings may be relevant to the aetiology of large bowel cancer.     

Simulated colon fiber metabolome regulates genes involved in cell cycle, apoptosis, and energy metabolism in human colon cancer cells

High level of dietary fiber has been epidemiologically linked to protection against the risk for developing colon cancer. The mechanisms of this protection are not clear. Fermentation of dietary fiber in the colon results in production of for example butyrate that has drawn attention as a chemopreventive agent. Polydextrose, a soluble fiber that is only partially fermented in colon, was fermented in an in vitro colon simulator, in which the conditions mimic the human proximal, ascending, transverse, and distal colon in sequence. The subsequent fermentation metabolomes were applied on colon cancer cells, and the gene expression changes studied. Polydextrose fermentation down-regulated gene ontology classes linked with cell cycle, and affected number of metabolically active cells. Furthermore, up-regulated effects on classes linked with apoptosis, with increased caspase 2 and 3 activity, implicate that polydextrose fermentation plays a role in induction of apoptosis in colon cancer cells. The up-regulated genes involved also key regulators of lipid metabolism, such as PPARα and PGC-1α. These results offer hypotheses for the mechanisms of two health benefits linked with consumption of dietary fiber, reducing risk of development of colon cancer, and dyslipidemia.     

Effect of oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione] on azoxymethane-induced biochemical changes related to early colon carcinogenesis in male F344 rats

Epidemiologic studies suggest that the consumption of cruciferous vegetables is associated with a reduced risk for several types of cancer including cancer of colon. Experimental studies indicate that dithiolthiones, naturally occurring substances in cruciferous vegetables, possess anticarcinogenic properties. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a substituted dithiolthione, has been tested for its chemopreventive activity. We studied the effect of dietary oltipraz on liver and colonic mucosal enzymes and DNA adducts to evaluate the modulating role of this agent during the early period of azoxymethane (AOM)-induced carcinogenesis. At 6 weeks of age, groups of animals were fed the AIN-76A diet containing 0 and 300 ppm oltipraz. At 8 weeks of age, all of the animals except vehicle-treated animals were administered a subcutaneous injection of AOM (15 mg/kg body wt/week for 2 weeks). Animals intended for vehicle treatment were administered normal saline subcutaneously. Fifteen hours after the second AOM injection, six animals each from control oltipraz diet groups were sacrificed and liver and colonic mucosa from each animal were used for DNA adduct analysis. Animals intended for liver and colonic mucosal glutathione S-transferase, tyrosine specific protein kinase (TPK), and ornithine decarboxylase (ODC) enzyme assays were killed 5 days after the second AOM or saline injection. The results of this study indicated that dietary oltipraz significantly increased liver (P less than 0.001) and colonic mucosal (P greater than 0.05) weights, but had no effect on body weights (P greater than 0.05). In saline-treated animals, feeding of oltipraz significantly increased the cytosolic glutathione S-transferase (P less than 0.001) and ODC (P less than 0.05) activities in the liver and colon when compared with those fed the control diet. Although our unpublished results indicate an inhibitory role of oltipraz when fed during the initiation and postinitiation phases of intestinal carcinogenesis, the increased ODC activity may indicate a possible role of oltipraz in colon tumor promotion. Additional studies are indicated to test the antitumor properties of oltipraz administered during the postinitiation phases. AOM treatment significantly increased the TPK (P less than 0.0001) and ODC (P less than 0.01) activities in the liver and colon of animals fed the control diet. Dietary oltipraz significantly suppressed the AOM-induced TPK (P less than 0.001) activities in liver and colon and ODC (P less than 0.01) activity of colon. Analysis of nucleic acid bases, O6-methylguanine, and 7-methylguanine revealed that dietary oltipraz significantly (P less than 0.05) inhibited the AOM-induced adduct species. These results suggest that dietary oltipraz enhances the colonic and liver glutathione S-transferase activity and reduced the formation of DNA adducts. In addition, dietary oltipraz modulates liver and colonic ODC and TPK activities that have been shown to play a role in tumor promotion.     

Effects of red meat and fiber in high fat diet on activities of sphingomyelinase,ceramidase and caspase-3 in rat colonic mucosa

Red meat and fiber rich foods are the dietary factors most consistently related to colon carcinogenesis. Although several components in these dietary sources may contribute, the biochemical mechanism by which red meat and fiber affect colorectal carcinogenesis has not yet been established. Sphingomyelin metabolism is a novel signal transduction pathway that may have an impact on colonic tumorigenesis. The present study investigated the activity changes of sphingomyelinase (SMase), ceramidase and caspase-3 in colonic mucosa of rats fed on a high fat control diet, the control diet with beef and the control diet with fiber (cellulose). After a three week feeding period the colonic mucosa were scraped and homogenized and enzyme activities were determined. The fiber diet significantly increased the activities of neutral and acid SMases but had no effect on those of alkaline SMase and neutral ceramidase. The beef diet, on the other hand, significantly reduced neutral ceramidase activity, but had no effect on the activities of any SMase. In addition, the beef diet significantly reduced and the fiber diet increased caspase-3 activity in the colonic mucosa when compared with the control diet. The changes of caspase-3 activities were abolished by preincubating the samples with caspase-3 inhibitor. No significant changes of intestinal alkaline phosphatase could be found among the three dietary groups. In conclusion, fiber and red meat in the high fat diet affected in an opposite way the enzymes responsible for sphingomyelin metabolism and apoptosis in the colon. The effects may have implications in colorectal tumorigenesis.     

Dietary fibre and colonic neoplasia.

Dietary plant fibre, or plantix, is thought to play a significant role in the pathogenesis of colon cancer in humans. It is a complex polymeric substance that has several distinct components resistant to hydrolysis by the digestive enzymes of humans. These components include cellulose, hemicelluloses, pectins, lignin, gums, mucilages and, in certain instances, algal polysaccharides. These polymers have different physicochemical properties, and recent evidence from experimental studies in animals treated with carcinogens suggests that some may exert protective effects in the intestine and others may enhance colon carcinogenesis. This review synthesizes information on the chemical composition, methods of analysis and physicochemical properties of dietary plant fibre and reviews available studies examining the role of fibre in colonic neoplasia in animals and humans.     

Dietary fiber, lipid metabolism, and atherosclerosis

Despite the physiochemical complexity of dietary fibers (plant cell walls) and their individual components, there is substantial epidemiologic, clinical, and experimental evidence that these dietary components may have a role in modifying certain risk factors in coronary heart disease. Particulate fibers, such as wheat bran, do not appear to significantly alter plasma lipids or lipoprotein distributions in humans, or the atherogenicity of diets in experimental animals. Dietary fibers found in fruits, legumes, and vegetables, in contrast, show more definitive responses. Among the fiber isolates, the gelling and mucilaginous fibers, such as pectins and guar gum, predictably decrease circulating lipids in humans and animals and increase excretion of fecal metabolites of cholesterol, the bile acids. These fibers and fiber components can be shown to influence luminal solubility of lipids and the extent of lymphatic absorption of both cholesterol and triglyceride. In addition, these same fibers are effective in reducing postprandial levels of glucose, insulin, and other hormones. These direct effects on lipid absorption, and secondary effects of glucose and insulin on hepatic and peripheral lipoprotein metabolism, can account for many of the hypolipidemic responses to specific dietary fibers or their components, and may be of long-term consequence in coronary heart disease.     

Fermentation of Fenugreek Fiber, Psyllium Husk, and Wheat Bran by Bacteroides ovatus V975

The objective of this study was to evaluate the ability of the human colonic bacterium Bacteroides ovatus V975 to ferment fenugreek fiber (Fenufibers™), psyllium husk (Metamucil?), and wheat bran (Wheat Chex). Strain V975 was incubated in basal medium that contained 0.1 g of each fiber source for 0, 24, or 48 h. Little digestion of either fiber source was detected over 48 h, and little acetate or succinate was produced. From the lack of significant fiber digestion and fermentation by B. ovatus, it seems that all three fiber sources could be used as dietary supplements to increase roughage in the human diet. Received: 30 April 1999 / Accepted: 24 June 1999     

Overlapping expression of microRNAs in human embryonic colon and colorectal cancer

MicroRNAs (miRNAs) are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, to date no evidence has linked miRNA expression in embryonic and tumor tissues. We assessed the expression of mature miRNAs in human embryonic colon tissue, and in colorectal cancer and paired normal colon tissue. Overlapping miRNA expression was detected between embryonic colonic mucosa and colorectal cancer. We have found that the miR-17-92 cluster and its target, E2F1, exhibit a similar pattern of expression in human colon development and colonic carcinogenesis, regulating cell proliferation in both cases. In situ hybridization confirmed the high level of expression of miR-17-5p in the crypt progenitor compartment. We conclude that miRNA pathways play a major role in both embryonic development and neoplastic transformation of the colonic epithelium.     

Livin及survivin表达与结肠癌发生、发展、转移及预后的关系

目的：探讨Livin及survivin表达与结肠癌发生、发展、转移及预后的关系。方法：采用免疫组化sP法检测100例结肠癌病人的癌、癌旁组织和正常结肠组织标本中Livin及survivin的表达,分析其与结肠癌发生、发展、转移及预后的关系,并通过随访研究其与5年生存率的关系。结果：Livin和Survivin在结肠癌组织中的阳性表达率均显著高于癌旁组织和正常结肠组织（P〈0．05）,在结肠癌组织中的表达与患者年龄、性别、肿瘤的大小和分化程度均不具有相关性（P〉O．05）,在有淋巴结及远处转移患者中高表达,与无转移者差异显著（P〈0．05）;Livin和Survivin表达阳性者5年生存率均明显低于表达阴性者（P〈0．05）;Livin和Survivin的表达无相关性。结论：Livin和Survivin在结肠癌的发生、发展和转移中起重要作用,对预后的判断具有一定的参考意义。     

Dietary astaxanthin inhibits colitis and colitis-associated colon carcinogenesis in mice via modulation of the inflammatory cytokines

Astaxanthin (AX) is one of the marine carotenoid pigments, which possess powerful biological antioxidant, anti-inflammatory and anti-cancer properties. The purpose of this study is to investigate possible inhibitory effect of AX against inflammation-related mouse colon carcinogenesis and dextran sulfate sodium (DSS)-induced colitis in male ICR mice. We conducted two different experiments. In the first experiment, we evaluated the effects of AX at three dose levels, 50, 100 and 200 ppm in diet, on colitis-associated colon carcinogenesis induced by azoxymethane (AOM)/DSS in mice. In the second, the effects of the AX (100 and 200 ppm) in diet on DSS-induced colitis were determined. We found that dietary AX significantly inhibited the occurrence of colonic mucosal ulcers, dysplastic crypts, and colonic adenocarcinoma at week 20. AX-feeding suppressed expression of inflammatory cytokines, including nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α and interleukin (IL)-1β, inhibited proliferation, and induced apoptosis in the colonic adenocarcinomas. Feeding with 200 ppm AX, but not 100 ppm, significantly inhibited the development of DSS-induced colitis. AX feeding (200 ppm in diet) also lowered the protein expression of NF-κB, and the mRNA expression of inflammatory cytokines, including IL-1β, IL-6, and cyclooxygenase (COX)-2. Our results suggest that the dietary AX suppresses the colitis and colitis-related colon carcinogenesis in mice, partly through inhibition of the expression of inflammatory cytokine and proliferation. Our findings suggest that AX is one of the candidates for prevention of colitis and inflammation-associated colon carcinogenesis in humans.     

Down-regulation of the tumor suppressor gene C-terminal Src kinase: an early event during premalignant colonic epithelial hyperproliferation

Hyperproliferation of the premalignant epithelium is critical for colonic carcinogenesis; however the mechanisms remain largely unexplored. We report herein that prior to occurrence of neoplastic lesions in the azoxymethane-rat model of colon carcinogenesis; the tumor suppressor gene C-terminal Src kinase (Csk) was down-regulated with a concomitant increase in Src activity. Furthermore, pharmacological or genetic (RNA interference) inhibition of Csk resulted in increased proliferation in colon cancer cell lines through the mitogen-activated protein kinase dependent pathway. Thus, we demonstrate, for the first time, that Csk suppression is an important early event in colorectal cancer pathogenesis.     

Signal transduction pathways leading to cell cycle arrest and apoptosis induction in cancer cells by Allium vegetable-derived organosulfur compounds: a review

Epidemiological studies continue to support the premise that dietary intake of Allium vegetables (e.g., garlic, onions and so forth) may lower the risk of various types of cancer. Anticarcinogenic effect of Allium vegetables is attributed to organosulfur compounds (OSCs) that are generated upon processing of these vegetables. Preclinical studies have provided convincing evidence to indicate that Allium vegetable-derived OSCs including diallyl sulfide, diallyl disulfide and diallyl trisulfide are highly effective in affording protection against cancer in laboratory animals induced by a variety of chemical carcinogens. Inhibition of carcinogen activation through modulation of cytochrome P450-dependent monooxygenases and/or acceleration of carcinogen detoxification via induction of phase II enzymes (glutathione transferases, quinone reductase, etc.) are believed to be responsible for protective effects of OSCs against chemically induced cancers. More recent studies have indicated that some naturally occurring OSC analogues can suppress proliferation of cancer cells in culture and inhibit growth of transplanted tumor xenografts in vivo by inducing apoptosis and/or by perturbing cell cycle progression. This review summarizes current knowledge on signal transduction pathways leading to perturbations in cell cycle progression and apoptosis induction by OSCs.     

Prevention of cancer and other chronic diseases worldwide based on sound mechanisms

The transformation of normal cells by DNA reactive, genotoxic carcinogens and the growth promotion and development of mutated cells by enhancing factors is involved in the overall basic mechanism of cancer induction. Thus, discrimination between genotoxic carcinogens and nongenotoxic chemicals is essential. The dose-response curves, reversibility, and organ-and species specificity are distinct. Genotoxic carcinogens are mutagenic, form DNA adducts, induce DNA repair, and form hydroxy radicals and inappropriate peroxidation reactions that antioxidants such as those in vegetables, fruits, and tea can decrease. In contrast, promoters do not form DNA adducts, but raise cell duplication rates, among other attributes. In the USA, about 35% of known cancers are associated with tobacco use and about 55% with inappropriate nutritional habits. Cancer induction can be decreased by avoiding the formation of carcinogens, reducing their metabolic activation, or increasing their detoxification. Excessive dietary salt, and heterocyclic arylamines formed in cooking of meats or fish, and high intake of 40% of calories in fats are health risks, but vegetables, fruits, tea, soy products, and fibers are protective. We review nutritional factors involved in cancer and chronic disease causation and prevention.