Abstract
Abstract Background: High red meat intake and meat-derived mutagen heterocyclic amines (HCAs) exposure have been linked to the risk of colorectal polyps and cancer. HCAs are activated and detoxified by a group of carcinogen metabolizing enzymes. Internal exposure dose to these carcinogens is determined by both external exposure and genetic polymorphisms in genes encoding these enzymes, providing a unique opportunity to conduct a Mendelian randomization analysis to reduce bias associated with observational epidemiological studies. Methods: In a colonoscopy-based case-control study, we recruited 5,386 participants, including 2,057 patients with colorectal polyps, and 3,329 polyp-free controls. Twenty single nucleotide polymorphisms (SNPs) were analyzed to construct a HCA metabolizing score. Data on dietary intake of meat by cooking methods and doneness level were obtained through telephone interviews to derive dietary HCA exposure level. Interactions between HCA metabolizing score and dietary exposure variables were evaluated using multivariate unconditional logistic regression models to derive odds ratios (ORs) and 95% confidence intervals (CIs). Results: HCA metabolizing score was unrelated to polyp risk among those with a low intake of total meat or red meat and low dietary HCA exposure. These dietary variables also tended to not be associated with polyp risk among those with a low HCA metabolizing score. Risks of polyps associated with meat intake and HCA exposure, however, were elevated among those with a high risk HCA metabolizing score. The interactions between dietary meat exposures and HCA metabolizing score were statistically significant for most of the analyses (P α0.05). Participants with the highest meat intake and HCA exposure level and a high risk HCA metabolizing score had a 30% to 40% elevated risk of developing any polyps and 60% to 80% elevated risk of developing advanced or multiple adenomas. Conclusions: Dietary meat intake and dietary exposure to HCAs is associated with an elevated risk of colorectal polyps, and this association is modified by genetic polymorphisms in HCA metabolizing enzymes. This study provides strong evidence supporting a causal role of HCA exposure in the etiology of colorectal tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4817. doi:1538-7445.AM2012-4817
Published Version
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