Meat intake, heterocyclic amine exposure, and metabolizing enzyme polymorphisms in relation to colorectal polyp risk.

摘要: Most colorectal cancers arise from adenomatous polyps or certain hyperplastic polyps. Only a few studies have investigated potential genetic modifiers of the associations between meat intake and polyp risk, results are inconsistent. Using data Tennessee Colorectal Polyp Study, large colonoscopy-based study, including 1,002 cases (557 adenoma only, 250 195 both polyps) 1,493 polyp-free patients, we evaluated association risk with carcinogen exposure polymorphisms in enzymes involved heterocyclic amine (HCA) metabolism, N-acetyltransferase 1 (NAT1) 2 (NAT2), cytochrome P450 1A2 (CYP1A2), aryl hydrocarbon receptor (AhR). Data on levels meats by preparation methods, doneness preferences, other lifestyle factors were obtained. Fourteen single nucleotide AhR, CYP1A2, NAT1, NAT2 genes evaluated. No clear was found for any risk. However, apparent interactions HCAs genotypes, statistically significant group Dose-response relationships HCA only among those AhR GA/AA (rs2066853) genotype, NAT1 rapid, rapid/intermediate acetylators but not genotypes these genes. This dose-response relationship more evident rapid acetylator than without this genotype combination. These provide strong evidence modifying effect metabolizing