Cigarette smoking, meat intake, and gene polymorphisms in relation to colorectal polyps risk.

B185

Most colorectal cancer arises from colorectal polyps, particularly adenomatous polyps. Although smoking and high meat intake have been linked to elevated risk of polyps, only a few studies have investigated potential genetic modifiers on these associations. We utilized samples from the Tennessee Colorectal Polyp Study (TCPS), a large colonoscopy-based case-control study to evaluate the association between genetic polymorphisms in genes (CYP1A2, NAT2, and AhR) involved in the metabolism of carcinogens high in well-done meat and cigarette smoke, such as heterocyclic amines (HCA) and colorectal polyp risk. Included in the current analysis are 1,110 polyp cases (601 with adenoma only, 290 with hyperplastic polyp only, 219 with concurrent adenoma and hyperplastic polyp) and 1,719 polyp-free controls. A telephone interview was conducted to obtain information on lifestyle factors including smoking and usual intake levels of 11 meats by cooking methods. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Cigarette smoking was a strong risk factor for adenoma and hyperplastic polyp. CYP1A2 genotypes were found to modify the smoking-related association only among patients with concurrent adenoma and hyperplastic polyps. In this group of patients, the odds ratios associated with regular cigarette smoking were 10.1 (95% CI = 4.9-20.7) among subjects with the AC or CC genotypes and 5.9 (95% CI = 3.2-11.0) among subjects with the AA genotype. A stronger association of smoking and concurrent adenoma and hyperplastic polyp risk was also observed among those who possessed NAT2 rapid or intermediate acetylators compared to subjects with the slow NAT2 genotypes. Similarly, NAT2 genotypes were found to modify the association of meat intake with polyp risk primarily among subjects with concurrent adenoma and hyperplastic polyps. A dose-response relation with meat intake was found among those with NAT2 rapid or intermediate acetylators (OR = 4.6, 95% CI = 1.4-14.5, highest quartile vs. lowest quartile of intake, p for trend = 0.012), but not among those with NAT2 slow acetylator. Our result suggests a potential effect modification of smoking and red meat intake by CYP1A2 and NAT2 polymorphisms on the risk of polyps, and risk factors for subjects with concurrent adenoma and hyperplastic polyp may differ from patients with only one type of these polyps.