Effect of NAT1 and NAT2 genetic polymorphisms on colorectal cancer risk associated with exposure to tobacco smoke and meat consumption.

N-Acetyltransferases 1 and 2 (NAT1 and NAT2), both being highly polymorphic, are involved in the metabolism of aromatic and heterocyclic aromatic amines present in cigarette smoke and red meat cooked by high-temperature cooking techniques. We investigated the effect of differences in acetylation capacity, determined by NAT1 and NAT2 genotypes, on colorectal cancer risk associated with exposure to tobacco smoke or red meat consumption. In this population-based case-control study in Germany, 505 patients with incident colorectal cancer and 604 age- and sex-matched control individuals with genotyping data and detailed risk factor information were included. Genotyping of NAT1 and NAT2 genetic polymorphisms was done using a fluorescence-based melting curve analysis method. The association between genotypes, environmental exposures, and colorectal cancer risk was estimated using multivariate logistic regression. Colorectal cancer risk associated with active smoking was elevated after accumulation of 30(+) pack-years of smoking [odds ratio (OR), 1.4; 95% confidence interval (95% CI), 0.9-2.2] but not significantly modified by either NAT1 or NAT2 genotype. Exposure to environmental tobacco smoke was associated with an increased risk for colorectal cancer only among NAT2 fast acetylators (OR, 2.6; 95% CI, 1.1-5.9 for exposure in childhood and adulthood). Frequent consumption of red meat significantly increased colorectal cancer risk for the group comprising all NAT2 fast acetylators or carriers of the NAT1*10 allele (OR, 2.6; 95% CI, 1.1-6.1) but not among those with "slow" NAT1 and NAT2 genotypes. Our findings indicate that NAT1 and NAT2 genotypes may contribute jointly to individual susceptibility and that heterocyclic aromatic amines may play an important role in colorectal cancer associated with red meat and possibly also exposure to environmental tobacco smoke.

Lilla C ，Verla-Tebit E ，Risch A ，Jäger B ，Hoffmeister M ，Brenner H ，Chang-Claude J ... -  《CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION》

Arylamine N-acetyltransferase 1 (NAT1) and 2 (NAT2) polymorphisms in susceptibility to bladder cancer: the influence of smoking.

Okkels H ，Sigsgaard T ，Wolf H ，Autrup H ... -  《CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION》

A prospective study of N-acetyltransferase genotype, red meat intake, and risk of colorectal cancer.

Chen J ，Stampfer MJ ，Hough HL ，Garcia-Closas M ，Willett WC ，Hennekens CH ，Kelsey KT ，Hunter DJ ... -  《CANCER RESEARCH》

Prospective study of NAT1 and NAT2 polymorphisms, tobacco smoking and meat consumption and risk of colorectal cancer.

Sørensen M ，Autrup H ，Olsen A ，Tjønneland A ，Overvad K ，Raaschou-Nielsen O ... -  《CANCER LETTERS》

Polyadenylation polymorphism in the acetyltransferase 1 gene (NAT1) increases risk of colorectal cancer.

Bell DA ，Stephens EA ，Castranio T ，Umbach DM ，Watson M ，Deakin M ，Elder J ，Hendrickse C ，Duncan H ，Strange RC ... -  《CANCER RESEARCH》