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Heterocyclic aromatic amine intake increases colorectal adenoma risk: findings from a prospective European cohort study.BACKGROUND: Heterocyclic aromatic amines (HCAs), which arise from cooking meat and fish at high temperatures, may increase the risk of colorectal adenomas. Conversely, flavonoids might counteract the negative effects of HCAs. OBJECTIVE: The association between dietary HCA intake and colorectal adenoma incidence was investigated in a prospective cohort study. DESIGN: At recruitment (1994-1998), detailed information on diet, anthropometric measures, lifestyle, and medication use was assessed in 25,540 participants of the European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort study. Dietary HCA intake was estimated by using information from food-frequency questionnaires on meat consumption, applied cooking methods, and preferred degree of browning. Until June 2007, 516 verified incident colorectal adenomas were identified. Participants with negative colonoscopy (n = 3966) were also included in the analytic cohort. Multivariate Cox proportional hazards regression was used to examine the association between colorectal adenoma risk and intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline (DiMeIQx). RESULTS: In multivariate analyses, the intake of PhIP as the most abundant dietary HCA was associated with an increased risk of colorectal adenoma (relative risk: 1.47; 95% CI: 1.13, 1.93; quartile 4 compared with quartile 1; P for trend = 0.002), but no statistically significant associations were observed for MeIQx and DiMeIQx intakes. In addition, adenoma risk also increased with the consumption of strongly or extremely browned meat (P for trend = 0.04). The association of PhIP intake with adenoma risk was most pronounced for small adenomas (P for trend = 0.01) and adenomas localized in the distal colon (P for trend = 0.002). CONCLUSION: The results of this first European cohort study support data from case-control studies of a positive association between HCA intake and colorectal adenoma risk.