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CYP2E1 is an enzyme involved in the metabolism of N-nitrosamines and other carcinogenic substances. Functional RsaI and 96-bp insertion polymorphisms in 5'-flanking region have drawn interest in relation to the risk of colorectal cancer. We investigated the relation of these genetic polymorphisms and colorectal adenoma, a well-established precursor lesion of colorectal cancer. Subjects were 455 cases of colorectal adenomas and 1,052 controls of normal colonoscopy among men receiving a preretirement health examination in the Self Defense Forces. Genotypes were determined by either PCR-RFLP or PCR method. Statistical adjustment was made for smoking, alcohol use, body mass index, physical activity, and others. Individuals with RsaI c2 allele showed a decreased risk of proximal colon adenomas; adjusted odds ratios (95% confidence interval) of proximal and distal adenomas for the c1/c2 or c2/c2 genotype versus c1/c1 was 0.61 (0.41-0.88) and 0.95 (0.71-1.27), respectively. CYP2E1 96-bp insertion allele was associated with an increased risk of large (&gt; or = 5 mm) adenomas; adjusted odds ratios (95% confidence interval) of large and small adenomas for having at least one insertion allele were 1.41 (1.03-1.94) and 0.94 (0.71-1.25), respectively. A suggestive effect modification was noted for alcohol consumption on the association between RsaI polymorphism and proximal adenomas (P(interaction) = 0.09) as well as on the association between 96-bp insertion and large adenomas (P(interaction) = 0.05). These findings indicate that variation in activity and inducibility of CYP2E1 contribute to the development of colorectal carcinogenesis.

Genetic Polymorphisms of CYP2E1 and Risk of Colorectal Adenomas in the Self Defense Forces Health Study