Vegetarianism, low meat consumption and the risk of colorectal cancer in a population based cohort study.

To study how a vegetarian or low meat diet influences the risk of colorectal cancer compared to a high meat diet, and to assess the explanatory role of factors associated with these diets. In the Netherlands Cohort Study - Meat Investigation Cohort (NLCS-MIC) (cohort of 10,210 individuals including 1040 self-defined vegetarians), subjects completed a baseline questionnaire in 1986, based on which they were classified into vegetarians (n = 635), pescetarians (n = 360), 1 day/week- (n = 1259), 2-5 day/week- (n = 2703), and 6-7 day/week meat consumers (n = 5253). After 20.3 years of follow-up, 437 colorectal cancer cases (307 colon, 92 rectal) were available. A non-significantly decreased risk of CRC for vegetarians, pescetarians, and 1 day/week compared to 6-7 day/week meat consumers was observed (age/sex adjusted Hazard Ratios (HR): 0.73(0.47-1.13), 0.80(0.47-1.39), and 0.72(0.52-1.00), respectively). Most of the differences in HR between these groups could be explained by intake of dietary fiber and soy products. Other (non-)dietary factors characteristic for a vegetarian or low meat diet had negligible individual effects, but attenuated the HRs towards the null when combined. Vegetarians, pescetarians, and 1 day/week meat eaters showed a non-significantly decreased risk of colorectal cancer compared to 6-7 day/week meat consumers, mainly due to differences in dietary pattern other than meat intake.

Dietary iron, iron homeostatic gene polymorphisms and the risk of advanced colorectal adenoma and cancer.

Dietary iron intake and variation in iron homeostasis genes may affect colorectal neoplasia risk. We conducted two nested case-control studies within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: one of advanced colorectal adenoma (1205 cases; 1387 controls) and one of colorectal cancer (370 cases; 401 controls). Iron intake was estimated with a food frequency questionnaire and genotyping was performed for 21 genes. Unconditional logistic regression was used to estimate odds ratio (OR) and 95% confidence intervals (95% CIs) for colorectal neoplasia risk within quartiles of intake. Several single nucleotide polymorphisms (SNPs) modified the association between iron intake and the risk of adenoma or cancer. Dietary iron was positively associated with colorectal adenoma among three SNPs of HEPHL1, including carriers of the AA genotype at rs7946162 (ORQ4-Q1 = 2.22, 95% CI 1.15-4.27, Ptrend = 0.03; Pinteraction = 0.10), the TT genotype at rs2460063 (ORQ4-Q1 = 2.39, 95% CI 1.26-4.54, Ptrend = 0.02; Pinteraction = 0.04) and the GG genotype at rs7127348 (ORQ4-Q1 = 2.40, 95% CI 1.23-4.67, Ptrend = 0.02; Pinteraction = 0.09). Heme iron was positively associated with colorectal cancer among those with GG genotypes for ACO1 rs10970985 (ORQ4-Q 1 = 2.45, 95% CI 3.40-8.06, Ptrend = 0.004; Pinteraction = 0.05). However, none of the associations were statistically significant after adjustment for multiple comparisons. Future studies should target the specific genes and SNPs for which the association was significant prior to multiple comparison correction.

The Netherlands Cohort Study−Meat Investigation Cohort; a population-based cohort over-represented with vegetarians, pescetarians and low meat consumers.

BACKGROUND: Vegetarian diets have been associated with lower risk of chronic disease, but little is known about the health effects of low meat diets and the reliability of self-reported vegetarian status. We aimed to establish an analytical cohort over-represented with vegetarians, pescetarians and 1 day/week meat consumers, and to describe their lifestyle and dietary characteristics. In addition, we were able to compare self-reported vegetarians with vegetarians whose status has been confirmed by their response on the extensive food frequency questionnaire (FFQ). STUDY METHODS: Embedded within the Netherlands Cohort Study (n = 120,852; including 1150 self-reported vegetarians), the NLCS-Meat Investigation Cohort (NLCS-MIC) was defined by combining all FFQ-confirmed-vegetarians (n = 702), pescetarians (n = 394), and 1 day/week meat consumers (n = 1,396) from the total cohort with a random sample of 2-5 days/week- and 6-7 days/week meat consumers (n = 2,965 and 5,648, respectively). RESULTS: Vegetarians, pescetarians, and 1 day/week meat consumers had more favorable dietary intakes (e.g., higher fiber/vegetables) and lifestyle characteristics (e.g. lower smoking rates) compared to regular meat consumers in both sexes. Vegetarians adhered to their diet longer than pescetarians and 1 day/week meat consumers. 75% of vegetarians with a prevalent cancer at baseline had changed to this diet after diagnosis. 50% of self-reported vegetarians reported meat or fish consumption on the FFQ. Although the misclassification that occurred in terms of diet and lifestyle when merely relying on self-reporting was relatively small, the impact on associations with disease risk remains to be studied. CONCLUSION: We established an analytical cohort over-represented with persons at the lower end of the meat consumption spectrum which should facilitate prospective studies of major cancers and causes of death using ≥20.3 years of follow-up.

Dietary heme iron and the risk of colorectal cancer with specific mutations in KRAS and APC.

Red meat intake has been linked to increased colorectal cancer (CRC) risk. Although the underlying mechanisms remain unclear, experimental studies suggest a role for dietary heme iron. Because heme iron was shown to promote specific mutations, it would be insightful to link heme iron data to CRC with mutations in key genes in an observational, population-based study. We investigated the association between dietary heme iron intake and risk of CRC with mutations in APC (adenomatous polyposis coli) and KRAS (Kirsten ras) and P53 overexpression in the Netherlands Cohort Study. After 7.3 years of follow-up, excluding the first 2.3 years due to incomplete coverage of the pathology registry and to avoid preclinical disease, adjusted hazard ratios (including adjustment for total meat) and 95% confidence intervals were calculated, using 4026 subcohort members (aged 55-69 years at baseline), 435 colon and 140 rectal cancer patients. When comparing the highest with the lowest tertile of intake, heme iron intake was associated with an increased risk of CRC harboring activating mutations in KRAS (hazard ratio = 1.71, 95% confidence interval: 1.15-2.57; P for trend = 0.03) and CRC without truncating mutations in APC (hazard ratio = 1.79, 95% confidence interval: 1.23-2.60; P for trend = 0.003). We observed a positive association between heme iron intake and the risk of CRC with activating G>A mutations in KRAS (P for trend = 0.01) and overall G>A mutations in APC (P for trend = 0.005). No associations were found with CRC harboring G>T mutations in KRAS/APC. Heme iron intake was positively associated with the risk of P53 overexpressed tumors but not with tumors without P53 overexpression (Pheterogeneity = 0.12). Heme iron intake was associated with an increased risk of colorectal tumors harboring G>A transitions in KRAS and APC and overexpression of P53. These novel findings suggest that alkylating rather than oxidative DNA-damaging mechanisms are involved in heme-induced colorectal carcinogenesis.

Meat-related mutagen exposure, xenobiotic metabolizing gene polymorphisms and the risk of advanced colorectal adenoma and cancer.

Meat mutagens, including heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs) and N-nitroso compounds (NOCs), may be involved in colorectal carcinogenesis depending on their activation or detoxification by phase I and II xenobiotic metabolizing enzymes (XME). Using unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), we examined the intake of five meat mutagens and >300 single nucleotide polymorphisms (SNPs) in 18 XME genes in relation to advanced colorectal adenoma (1205 cases and 1387 controls) and colorectal cancer (370 cases and 401 controls) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary intake of meat mutagens was assessed using a food frequency questionnaire with a detailed meat-cooking module. An interaction was observed between 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) intake and the NAT1 polymorphism rs6586714 in the adenoma study (P(interaction) = 0.001). Among individuals carrying a GG genotype, high MeIQx intake was associated with a 43% increased risk of adenoma (95% CI 1.11-1.85, P(trend) = 0.07), whereas the reverse was observed among carriers of the A variant (OR = 0.50, 95% CI 0.30-0.84, P(trend) = 0.01). In addition, we observed some suggestive (P < 0.05) modifying effects for SNPs in other XME genes (UGT1A, CYP2E1, EPHX1, AHR and GSTM3), but these were not significant after adjustment for multiple testing. This large and comprehensive study of XME genes, meat mutagens and the risk of colorectal tumours found that a NAT1 polymorphism modified the association between MeIQx intake and colorectal adenoma risk.

Longitudinal changes in BMI in older adults are associated with meat consumption differentially, by type of meat consumed.

Hypotheses regarding the role of meat consumption in body weight modulation are contradictory. Prospective studies on an association between meat consumption and BMI change are limited. We assessed the association between meat consumption and change in BMI over time in 3902 men and women aged 55-69 y from the Netherlands Cohort Study. Dietary intake was estimated at baseline using a FFQ. BMI was ascertained through baseline self-reported height (1986) and weight (1986, 1992, and 2000). Analyses were based on sex-specific categories of daily total fresh meat, red meat, beef, pork, minced meat, chicken, processed meat, and fish consumption at baseline. Linear mixed effect modeling adjusted for confounders was used to assess longitudinal associations. Significant cross-sectional differences in BMI between quintiles of total meat intake were observed (P-trend < 0.01; both sexes). No association between total fresh meat consumption and prospective BMI change was observed in men (BMI change highest vs. lowest quintile after 14 y: -0.06 kg/m²; P = 0.75) and women (BMI change: 0.26 kg/m²; P = 0.20). Men with the highest intake of beef experienced a significantly lower increase in BMI after 6 and 14 y than those with the lowest intake (BMI change after 14 y 0.60 kg/m²). After 14 y, a significantly higher increase in BMI was associated with higher intakes of pork in women (BMI change highest vs. lowest quintile: 0.47 kg/m²) and chicken in both sexes (BMI change highest vs. lowest category in both men and women: 0.36 kg/m²). The results remained similar when stratifying on median baseline BMI, and age-stratified analyses yielded mixed results. Differential BMI change effects were observed for several subtypes of meat. However, total meat consumption, or factors directly related to total meat intake, was not strongly associated with weight change during the 14-y prospective follow-up in this elderly population.

Consumption of dietary fat and meat and risk of ovarian cancer in the Netherlands Cohort Study.

BACKGROUND: Evidence that links dietary factors to ovarian cancer is conflicting, but several epidemiologic studies suggested that consumption of dietary fat and meat may increase risk of ovarian cancer. OBJECTIVE: We studied associations of intakes of total fat and sources and subtypes of fat, fresh meat, processed meat, and fish with ovarian cancer risk within the Netherlands Cohort Study (NLCS). DESIGN: The NLCS includes 62,573 postmenopausal women, aged 55-69 y at baseline, who completed a baseline questionnaire on dietary habits and other risk factors for cancer in 1986. After 16.3 y of follow-up, 340 ovarian cancer cases and 2161 subcohort members were available for a case-cohort analysis. Multivariable rate ratios (RRs) were adjusted for age at baseline, total energy intake, oral contraceptive use, and parity. RESULTS: There were no clear associations between intakes of total fat, saturated fat, mono- and polyunsaturated fats, animal fat, plant-based fat, dairy fat, other fat sources, fresh meat, processed meat, and fish and ovarian cancer risk. There was a positive association between consumption of trans unsaturated fatty acids and ovarian cancer risk. The multivariable RR for women in the highest compared with the lowest quintiles of intake was 1.51 (95% CI: 1.04, 2.20; P for trend = 0.01). Although no significant interactions by oral contraceptive use or parity were shown, effect sizes were generally more pronounced and significant in women who never used oral contraceptives and in parous women. CONCLUSION: This prospective study suggests that trans unsaturated fatty acids, but no other types of fat or meat, are associated with increased ovarian cancer risk.