Polyadenylation Polymorphism in the Acetyltransferase 1 Gene (NATI) Increases Risk of Colorectal Cancer
نویسندگان
چکیده
Exposure to carcinogens present in the diet, cigarette smoke, or the environment may be associated with increased risk of coloréela!cancer. Aromatic amines (aryland heterocyclic) are a class of carcinogens that are important in these exposures. These compounds can be Nor 0-acetylated by the NATI or NAT2 enzymes, resulting in activation or in some cases detoxification. Recent studies have shown that both NAT2 and NATI genes exhibit variation in human populations and that rapid acetylation by the NAT2 enzyme may be a risk factor for coloréela!cancer. In this study we have analyzed for genetic polymorphism in both At Tl and NAT2 in a group of 202 colorectal cancer patients and 112 control subjects from Staffordshire, England. We find significantly increased risk (odds ratio, 1.9; 95% confidence interval, 1.2-3.2; P = 0.009) associated with the NATl*10 alÃ-eleof NATI, an alÃ-elethat contains a variant polyadenylation signal. Individuals with higher stage tumors (Duke's C) were more likely to inherit this variant alÃ-ele(odds ratio, 2.5; 95% confidence interval, 1.3—4.7;P = 0.005). In contrast, rapid acetylation genotypes of NAT2 were not a significant risk factor in this English population. However, we found that the risk associated with the NATI variant alÃ-ele(NATI*10) was most apparent among NAT2 rapid acetylators (odds ratio, 2.8; 95% confidence interval, 1.4-5.7; /' = 0.003), suggesting a possible gene-gene interaction between NATI and NA T2 (test for interaction; P = 0.12). This is the first study to test for cancer risk associated with the NATI gene, and these positive findings suggest that VI77 alÃ-eles may be important genetic determinents of colorectal cancer risk.
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تاریخ انتشار 2006