Laboratory data increasingly suggest that Salmonella infection may contribute to colon cancer (CC) development. Here, we examined epidemiologically the potential risk of CC associated with salmonellosis in the human population. We conducted a population-based cohort study using four health registries in Denmark. Person-level demographic data of all residents were linked to laboratory-confirmed non-typhoidal salmonellosis and to CC diagnoses in 1994–2016. Hazard ratios (HRs) for CC (overall/proximal/distal) associated with reported salmonellosis were estimated using Cox proportional hazard models. Potential effects of serovar, age, sex, inflammatory bowel disease and follow-up time post-infection were also assessed. We found no increased risk of CC ≥1 year post-infection (HR 0.99; 95% confidence interval (CI) 0.88–1.13). When stratifying by serovar, there was a significantly increased risk of proximal CC ≥1 year post-infection with serovars other than Enteritidis and Typhimurium (HR 1.40; 95% CI 1.03–1.90). CC risk was significantly increased in the first year post-infection (HR 2.08; 95% CI 1.48–2.93). The association between salmonellosis and CC in the first year post-infection can be explained by increased stool testing around the time of CC diagnosis. The association between proximal CC and non-Enteritidis/non-Typhimurium serovars is unclear and warrants further investigation. Overall, this study provides epidemiological evidence that notified Salmonella infections do not contribute significantly to CC risk in the studied population.

The health benefits of fruit, vegetables and dietary fibre have been promoted for many years. Much of the supporting evidence is circumstantial or even contradictory and mechanisms underlying health benefits of specific foods are poorly understood. Colorectal cancer shows marked geographical differences in incidence, probably linked with diet, and explanations for this require knowledge of the complex interactions between diet, microbiota and the gut epithelium. Dietary fibres can act as prebiotics, encouraging growth of saccharolytic bacteria, but other mechanisms are also important. Some but not all soluble fibres have a ‘contrabiotic’ effect inhibiting bacterial adherence to the epithelium. This is particularly a property of pectins (galacturonans) whereas dietary fructans, previously regarded as beneficial prebiotics, can have a proinflammatory effect mediated via toxic effects of high butyrate concentrations. This also suggests that ulcerative colitis could in part result from potentially toxic faecal butyrate concentrations in the presence of a damaged mucus layer. Epithelial adherence of lectins, either dietary lectins as found in legumes, or bacterial lectins such as the galactose-binding lectin expressed by colon cancer-associated Fusobacterium nucleatum, may also be important and could be inhibitable by specific dietary glycans. Conversely, emulsifiers in processed foods may increase bacterial translocation and alter the microbiota thus promoting inflammation or cancer. Focusing on one condition is of limited value although in developing public health messages and growing evidence for impacts of dietary components on all-cause mortality is gaining more attention. We are only just starting to understand the complex interactions between food, the microbiota and health.

An 80-year-old man was seen in urgent neuro-ophthalmology consultation for bilateral vision loss. He had a past medical history of hypertension and metastatic stage IV colorectal adenocarcinoma. Four months prior to presentation, he developed gradual onset, painless blurred vision in his right eye. He underwent cataract surgery in that eye, but his vision continued to decline to the point of no light perception. He developed new onset, painless, blurred vision in his left eye 3 weeks prior to presentation and woke up with no light perception in his left eye one day prior to presentation.

The role of environmental factors and genetic susceptibility in the development of colon cancer (CC) has been already proven, but the role of gene polymorphisms in modifying the risk of environmental factors such as nutritional factors is still unknown. This study aimed to investigate the effect of polymorphisms of involved genes in the association between red meat consumption and the development of CC. The present review was carried out using keywords such as polymorphism and/or protein and/or red meat and/or processed meat and/or colon cancer. PubMed and Science Direct databases were used to collect all related articles published from 2001 to 2017. The presence of SNP in the coding genes of proteins involved in metabolism of nutrients could play significant roles in the extent of the effects of nutrition in the development of CC. The effect of dietary proteins greatly depends on the polymorphisms in the metabolising genes of these substances. Gene polymorphisms may have a role in colorectal cancer risk, especially in people with high meat intake, and this leads to a difference in the effects of meat consumption in different individuals. To conclude, dietary recommendations for the prevention and control of CC should be modified based on the genotype of different individuals. Increasing our knowledge on this field of nutritional genomics can lead to personalised preventive and therapeutic recommendations for CC patients.

This paper assesses the likelihood that the Iran-Contra scandal was shaped heavily by the effects of Ronald Reagan's cancer surgery in summer, 1985. During the President's hospitalization and in the period soon after, he took several actions—which he apparently did not remember—that launched a policy that was unwise, counterproductive, and a failure. These damaged both his Administration and his standing in history. The 25th Amendment afforded Reagan the means by which his involvement in these events could easily have been avoided. However, the President and his aides determined that he would resume the powers and duties of the presidency only hours after undergoing extensive cancer surgery. This decision contributed materially to the most damaging episode of Reagan's eight-year presidency.

Fruit antioxidants have many health benefits including prevention of cancer development. The native Australian bush fruit Illawarra plum (Podocarpus elatus Endl., Podocarpaceae) has a high content of anthocyanin-rich phenolics, with an antioxidant capacity at levels higher than most fruits. In the present study the molecular mechanisms of the anti-proliferative activity of Illawarra plum on colorectal cancer cells were investigated. Non-tumorigenic young adult mouse colonic (YAMC) cells and tumorigenic human colonic (HT-29) cells were treated with a polyphenolic-rich Illawarra plum extract (0–1000 μg/ml). Illawarra plum had anti-proliferative properties in only the cancer cells, with growth suppressed in a dose- and time-dependent manner. Treatment of HT-29 cells with Illawarra plum extract (500 μg/ml; 24 h) was also associated with a 2-fold increase in apoptosis, and a cell cycle delay in the S phase (P< 0·01). Assessment of biomarkers for DNA damage revealed that plum treatment caused a 93 % down-regulation of telomerase activity (P< 0·001) and a decrease in telomere length (up to 75 %; P< 0·01). Treatment with Illawarra plum extract also induced morphological alterations to HT-29 cells that were suggestive of induction of autophagy, as the formation of cytoplasmic vacuoles was observed in many cells. This could be induced by the increased (6-fold) histone deacetylase (HDAC) activity (P< 0·001) and the trend for increased expression of the class III HDAC sirtuin 1. The present study has shown that Illawarra plum extract is able to reduce the proliferation of colon cancer cells by altering the cell cycle, increasing apoptosis and possibly inducing autophagy. The active ingredients in Illawarra plum may provide an alternative chemoprevention strategy to conventional chemotherapy.

Colorectal cancer is one of the most common causes of morbidity and mortality in Western countries, the second cause of cancer mortality in the USA and a major public health problem in Mexico. A diet rich in legumes is directly related to the prevention of colon cancer, showing an inverse relationship with the development of colorectal adenomas in human subjects. The present study shows the results of molecular changes involved in the Tp53 pathway at an early stage in the distal colon tissue of azoxymethane (AOM)-induced colon cancer in rats evaluated by PCR array after exposure to diets containing the non-digestible fraction (NDF) of cooked bean (cultivar Bayo Madero). Significant differences were detected in seventy-two genes of the Tp53-mediated signalling pathway involved in apoptosis, cell-cycle regulation and arrest, inhibition of proliferation and inflammation, and DNA repair. Tp53, Gadd45a, Cdkn1a and Bax were highly expressed (9·3-, 18·3-, 5·5- and 3·5-fold, respectively) in the NDF+AOM group, whereas Cdc25c, Ccne2, E2f1 and Bcl2 were significantly suppressed ( − 9·2-, − 2·6-, − 18·4- and − 3·5-fold, respectively), among other genes, compared with the AOM group, suggesting that chemoprevention of aberrant crypt foci results from a combination of cell-cycle arrest in G1/S and G2/M phases and cell death by apoptotic induction. We demonstrate that the NDF from common bean modulates gene expression profiles in the colon tissue of AOM-induced rats, contributing to the chemoprotective effect of common bean on early-stage colon cancer.

Inflammatory bowel disease (IBD) is a risk factor for the development of colon cancer. Environmental factors including diet and the microflora influence disease outcome. Folate and homocysteine have been associated with IBD-mediated colon cancer but their roles remain unclear. We used a model of chemically induced ulcerative colitis (dextran sodium sulphate (DSS)) with or without the colon carcinogen azoxymethane (AOM) to determine the impact of dietary folic acid (FA) on colonic microflora and the development of colon tumours. Male mice (n 15 per group) were fed a FA-deficient (0 mg/kg), control (2 mg/kg) or FA-supplemented (8 mg/kg) diet for 12 weeks. Folate status was dependent on the diet (P< 0·001) and colitis-induced treatment (P= 0·04) such that mice with colitis had lower circulating folate. FA had a minimal effect on tumour initiation, growth and progression, although FA-containing diets tended to be associated with a higher tumour prevalence in DSS-treated mice (7–20 v. 0 %, P= 0·08) and the development of more tumours in the distal colon of AOM-treated mice (13–83 % increase, P= 0·09). Folate deficiency was associated with hyperhomocysteinaemia (P< 0·001) but homocysteine negatively correlated with tumour number (r − 0·58, P= 0·02) and load (r − 0·57, P= 0·02). FA had no effect on the intestinal microflora. The present data indicate that FA intake has no or little effect on IBD or IBD-mediated colon cancer in this model and that hyperhomocysteinaemia is a biomarker of dietary status and malabsorption rather than a cause of IBD-mediated colon cancer.

Colorectal cancer (CRC) is a multi-factorial disease in which diet is believed to play a role. Little is known about the health effects of specific regional diets. The Nordic diet is high in fat and sugar but also includes a range of traditional products with anticipated health-promoting effects. The aim of this cohort study was to determine whether a healthy Nordic food index consisting of fish, cabbage, rye bread, oatmeal, apples, pears and root vegetables was related to CRC incidence. Data were obtained from a prospective cohort study of 57 053 Danish men and women aged 50–64 years, of whom 1025 developed CRC (13 years' follow-up). Incidence rate ratios (IRR) with 95 % CI were calculated from Cox proportional hazard models. Women who strongly adhered to a healthy Nordic food index had a 35 % lower incidence of CRC than women with poor adherence (adjusted IRR, 0·65; 95 % CI 0·46, 0·94); a similar tendency was found for men. Women had a 9 % lower incidence of CRC per point adherence to the healthy Nordic food index, but no significant effect was found for men. A regional diet based on healthy Nordic food items was therefore associated with a lower incidence of CRC in women. The protective effect was of the same magnitude as previously found for the Mediterranean diet, suggesting that healthy regional diets should be promoted in order to ensure health; this will also preserve cultural heredity and the environment.

The present study aimed to explore the role(s) of the soya isoflavone genistein (GEN) in preventing the development of colon pre-neoplasia, using Wingless/int (WNT)/β-catenin as a molecular marker of colon abnormality. Specifically, the effects on the WNT/β-catenin signalling pathway from GEN were examined by using an azoxymethane (AOM)-induced rat colon cancer model. Male Sprague–Dawley rats were fed a control (CTL), a soya protein isolate (SPI) or a GEN diet from gestation to 13 weeks of age. The first sampling was conducted at 7 weeks of age for pre-AOM analysis. The remaining rats were injected with AOM at 7 weeks of age. The descending colon was collected 6 weeks later for the evaluation of aberrant crypt foci (ACF), gene expression and nuclear protein accumulation. AOM injection induced aberrant nuclear accumulation of β-catenin in the CTL group but not in the SPI or GEN group. Moreover, the WNT target genes Cyclin D1 and c-Myc were repressed by SPI and GEN. Meanwhile, SPI and GEN suppressed the expression of WNT signalling genes including Wnt5a, Sfrp1, Sfrp2 and Sfrp5 to the similar level to that of the pre-AOM period. Rats fed SPI and GEN had a decreased number of total aberrant crypts. GEN feeding also resulted in a reduced number of ACF with N = 3 per foci. The reduction of WNT/β-catenin signalling was correlated with the decrease in total aberrant crypts. By testing WNT/β-catenin signalling as a biomarker of colon carcinogenic potential, we showed the novel role of GEN as a suppressor of carcinogen-induced WNT/β-catenin signalling in preventing the development of early colon neoplasia.

Obesity is linked to increased risk of colon cancer, currently the third most common cancer. Consequently rising levels of obesity worldwide are likely to significantly impact on obesity-related colon cancers in the decades to come. Understanding the molecular mechanisms whereby obesity increases colon cancer risk is thus a focus for research to inform strategies to prevent the increasing trend in obesity-related cancers. This review will consider research on deregulation of adipokine signalling, a consequence of altered adipokine hormone secretion from excess adipose tissue, with a focus on leptin, which has been studied extensively as a potential mediator of obesity-related colon cancer. Numerous investigations using colon cell lines in vitro, in vivo studies in rodents and investigations of colon cancer patients illuminate the complexity of the interactions of leptin with colon tissues via leptin receptors expressed by the colon epithelium. Although evidence indicates a role for leptin in proliferation of colon epithelial cells in vitro, this has been contradicted by studies in rodent models. However, recent studies have indicated that leptin may influence inflammatory mediators linked with colon cancer and also promote cell growth dependent on genotype and is implicated in growth promotion of colon cancer cells. Studies in human cancer patients indicate that there may be different tumour sub-types with varying levels of leptin receptor expression, indicating the potential for leptin to induce variable responses in the different tumour types. These studies have provided insights into the complex interplay of adipokines with responsive tissues prone to obesity-related colon cancer. Deregulation of adipokine signalling via adipokine receptors located in the colon appears to be a significant factor in obesity-related colon cancer. Molecular profiling of colon tumours will be a useful tool in future strategies to characterise the influence that adipokines may have on tumour development and subsequent therapeutic intervention. Study of the molecular mechanisms linking obesity with cancer also supports recommendations to maintain a normal body weight to reduce the risk of colon cancer.

Several studies have suggested that the partially fermentable fibre Plantago ovata husk (PO) may have a protective effect on colorectal cancer (CRC). We studied the potentially pro-apoptotic effect of PO and the implicated mechanisms in CRC cells with different molecular phenotypes (Caco-2, HCT116, LoVo, HT-29, SW480) after PO anaerobic fermentation with colonic bacteria as it occurs in the human colon. The fermentation products of PO induced apoptosis in all primary tumour and metastatic cell lines, independent of p53, adenomatous polyposis coli, β-catenin or cyclo-oxygenase-2 status. Apoptosis was caspase-dependent and both intrinsic and extrinsic pathways were implicated. The intrinsic pathway was activated through a shift in the balance towards a pro-apoptotic environment with an up-regulation of B-cell lymphoma protein 2 homologous antagonist killer (BAK) and a down-regulation of B-cell lymphoma-extra large (Bcl-xL) seen in HCT116 and LoVo cells. This resulted in mitochondrial membrane depolarisation, increased expression of caspase activators second mitochondria-derived activator of caspases (Smac)/Diablo, death effector apoptosis-inducing factor, apoptosome member apoptotic protease activating factor 1 and down-regulation of inhibitors of apoptosis Survivin and X-linked inhibitor of apoptosis in most cells. The extrinsic pathway was activated presumably through the up-regulation of death receptor (DR5). Some important differences were seen between primary tumour and metastatic CRC cells. Thus, metastatic PO-treated LoVo cells had a remarkable up-regulation of TNF-α ligand along with death-inducing signalling complex components receptor interacting protein and TNF-α receptor 1-associated death domain protein. The extrinsic pathway modulator FCICE-inhibitory protein (FLIP), an inhibitor of both spontaneous death ligand-independent and death receptor-mediated apoptosis, was significantly down-regulated after PO treatment in all primary tumour cells, but not in metastatic LoVo. These findings suggest that PO could potentially be a useful chemotherapy adjuvant.

Tumors consist of a heterogeneous population of neoplastic cells infiltrated by an equally heterogeneous collection of nonneoplastic cells that comprise the tumor microenvironment. Tumor growth, invasion, and metastasis depend on multiple interactions between these cells. To assess their potential as therapeutic targets or vehicles for tumor specific delivery of therapeutic agents, we examined the contribution of bone marrow derived cells (BMDCs) to the intestinal tumor microenvironment. Hematopoietic stem cells expressing the enhanced green fluorescent protein (eGFP) were transplanted into lethally irradiated ApcMin/+ mice, and their engraftment was analyzed by confocal microscopy. The results showed abundant infiltration of eGFP cells into the small intestine, colon, and spleen compared to heart, muscle, liver, lung, and kidney. Within the intestine, there was a pronounced gradient of engraftment along the anterior to posterior axis, with enhanced infiltration into adenomas. Immunofluorescence analysis showed that osteopontin was expressed in tumor stromal cells but not in nontumor stromal populations, suggesting that gene expression in these cells is distinct. Tumor vasculature in ApcMin/+ mice was chaotic compared to normal intestinal regions. Our data suggest that BMDCs can be harnessed for tumor-targeted therapies to enhance antitumor efficacy.

Epigenetic changes are inherited alterations in DNA that affect gene expression and function without altering the DNA sequence. DNA methylation is one epigenetic process implicated in human disease that is influenced by diet. DNA methylation involves addition of a 1-C moiety to cytosine groups in DNA. Methylated genes are not transcribed or are transcribed at a reduced rate. Global under-methylation (hypomethylation) and site-specific over-methylation (hypermethylation) are common features of human tumours. DNA hypomethylation, leading to increased expression of specific proto-oncogenes (e.g. genes involved in proliferation or metastasis) can increase the risk of cancer as can hypermethylation and reduced expression of tumour suppressor (TS) genes (e.g. DNA repair genes). DNA methyltransferases (DNMT), together with the methyl donor S-adenosylmethionine (SAM), facilitate DNA methylation. Abnormal DNA methylation is implicated not only in the development of human cancer but also in CVD. Polyphenols, a group of phytochemicals consumed in significant amounts in the human diet, effect risk of cancer. Flavonoids from tea, soft fruits and soya are potent inhibitors of DNMT in vitro, capable of reversing hypermethylation and reactivating TS genes. Folates, a group of water-soluble B vitamins found in high concentration in green leafy vegetables, regulate DNA methylation through their ability to generate SAM. People who habitually consume the lowest level of folate or with the lowest blood folate concentrations have a significantly increased risk of developing several cancers and CVD. This review describes how flavonoids and folates in the human diet alter DNA methylation and may modify the risk of human colon cancer and CVD.

Epidemiological evidence suggests that the intake of prebiotic dietary fibres, for example, inulin, protects against colorectal cancer. However, little is known about cellular responses to complex fermentation samples. Therefore, we prepared a fermentation supernatant fraction of inulin and studied biological properties in human colon cell lines, LT97 and HT29 (representing early and late stages of colon cancer). Inulin enriched with oligofructose (Synergy 1) was incubated under anaerobic conditions with faecal inocula and the supernatant fraction was characterised for content of SCFA and secondary bile acid deoxycholic acid (DCA). A Synergy fermentation supernatant fraction (SFS) and a synthetic fermentation mixture (SFM) mimicking the SFS in SCFA and DCA content were used in the concentration range of 1·25–20 % (v/v) for 24–72 h. The effects on cell growth were determined by quantifying DNA. Effects on apoptosis were analysed by measuring poly(ADP-ribose) polymerase (PARP) cleavage using Western blotting. Compared with the faecal blank, produced without the addition of inulin, the SFS resulted in an almost 2·5-fold increase of SCFA and 3·4-fold decrease of DCA. In comparison with HT29 cells, LT97 cells responded more sensitively to the growth-inhibitory activities. Additionally, a significant increase in PARP cleavage was observed in LT97 cells after incubation with the SFS, demonstrating induction of apoptosis. The present results indicate growth-inhibiting and apoptosis-inducing effects of fermentation supernatant fractions of inulin. Moreover, since early adenoma cells were found to be more sensitive, this may have important implications for chemoprevention when translated to the in vivo situation, because survival of early transformed cells could be reduced.

Fermentation of dietary fibre by the gut microflora may enhance levels of SCFA, which are potentially chemoprotective against colon cancer. Functional food containing wheat aleurone may prevent cancer by influencing cell cycle and cell death. We investigated effects of fermented wheat aleurone on growth and apoptosis of HT29 cells. Wheat aleurone, flour and bran were digested and fermented in vitro. The resulting fermentation supernatants (fs) were analysed for their major metabolites (SCFA, bile acids and ammonia). HT29 cells were treated for 24–72 h with the fs or synthetic mixtures mimicking the fs in SCFA, butyrate or deoxycholic acid (DCA) contents, and the influence on cell growth was determined. Fs aleurone was used to investigate the modulation of apoptosis and cell cycle. The fermented wheat samples contained two- to threefold higher amounts of SCFA than the faeces control (blank), but reduced levels of bile acids and increased concentrations of ammonia. Fs aleurone and flour equally reduced cell growth of HT29 more effectively than the corresponding blank and the SCFA mixtures. The EC50 (48 h) ranged from 10 % (flour) to 19 % (blank). Markedly after 48 h, fs aleurone (10 %) significantly induced apoptosis and inhibited cell proliferation by arresting the cell cycle in the G0/G1 phase. In conclusion, fermentation of wheat aleurone results in a reduced level of tumour-promoting DCA, but higher levels of potentially chemopreventive SCFA. Fermented wheat aleurone is able to induce apoptosis and to block cell cycle – two essential markers of secondary chemoprevention.

The mechanism that drives the growth of some colonic adenomas towards malignancy, while permitting others to remain for decades in quiescence, remains unknown. Diets can alter the growth rate of intestinal tumours but it is still unknown whether diets are able to alter the molecular biology of these adenomas in a way that predicts further outcome. To address this issue we fed Min/+ mice with two diets known to lead to different adenoma outcomes: a high-fat control diet (n 15) or a high-fat inulin-enriched (10 % w/w) diet (n 13). To study the effect of diet on cell signalling during adenoma growth, the adenomas of each Min/+ mouse were divided into three size-categories, and the levels of β-catenin, E-cadherin, cyclin D1 and matrix metalloproteinase-9, which are known to be involved in colon tumorigenesis, were determined. The growth-promoting inulin diet resulted in more large adenomas than the control feeding (P = 0·003) and doubled the total area of the adenomas (P = 0·008). The inulin diet increased the expression of nuclear β-catenin (P = 0·004) and its target cyclin D1 (P = 0·017) as the adenomas increased in size from small to large, indicating the presence of an accelerated cancerous process. Neither phenomenon was seen in the control group during adenoma growth. Our results suggest that in addition to the number, size, and growth rate of adenomatous polyps, the signalling pattern of the adenomas should also be considered when evaluating preventive dietary strategies.

While several effects beneficial to health have been attributed to the probiotic lactic acid bacteria, perhaps the most interesting and controversial remains that of anti-cancer activity. The vast majority of studies in this area deal with protective effects against colon cancer. There is no direct experimental evidence for cancer suppression in human subjects as a result of the consumption of probiotic cultures in fermented or unfermented dairy products. However, there is a wealth of indirect evidence, based largely on laboratory studies. Reports in the literature, regarding the anti-cancer effects of lactic acid bacteria, fall into the following categories: in vitro studies, animal studies, epidemiological studies and human dietary intervention studies. Examples of these reports will be given in the present review. The mechanisms by which probiotic bacteria may inhibit colon cancer are still poorly understood. However, several potential mechanisms are being discussed in the literature and these will also be addressed in the present review.

Lactic acid bacteria (LAB) are present in many foods such as yoghurt and are frequently used as probiotics to favour some biological functions in the host. Many investigators have evaluated the therapeutic effects of yoghurt and LAB commonly used in yoghurt production against diseases such as cancer, infection, and gastrointestinal disorders. The increase of immune cell activity in the prevention of cancer by LAB consumption has also been described. Another possible explanation for the preventive effect of probiotics on carcinogenesis is their effect on other bacteria in the intestine. Probiotics may suppress the growth of bacteria that convert procarcinogens into carcinogens, thereby reducing the amount of carcinogens in the intestine. The present review is focused on two types of cancer in which milk fermented by LAB may show a beneficial effect: colon cancer and breast cancer

Recent studies have shown a decreased risk of colon cancer with consumption of fish. However, most studies on fish consumption do not distinguish between lean and fatty fish, or between poached and fried fish. The aim of this study was to investigate any association between fish consumption and colon cancer in The Norwegian Women and Cancer (NOWAC) study. We focused mainly on lean fish, which was further divided into poached and fried fish. A total of 63 914 women were included in the analysis, 254 of whom were found to have colon cancer during follow-up. Since fish consumption was one of the main topics of interest in the NOWAC study, there is a predominance of women from northern Norway due to higher fish intake in this area; hence the study is not representative of the whole of Norway. The participants completed a semi-quantitative FFQ between 1996 and 1999, and were followed-up for incidence of colon cancer until 2004. No association between fish consumption and risk of colon cancer was seen, except for the third tertile of poached lean fish consumption (relative risk (RR) 1·46, 95 % CI 1·04, 2·06). This association disappeared when excluding women with less than 1 year of follow-up. In conclusion, the present study does not support the hypothesis of a protective effect of fish against colon cancer risk.