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

¹ Department of Preventive Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan; ² Self-Defense Forces Fukuoka Hospital, Kasuga, Japan; and ³ Self Defense Forces Kumamoto Hospital, Kumamoto, Japan

Requests for reprints: Makiko Morita, Department of Preventive Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Phone: 81-92-642-6112; Fax: 81-92-642-6115. E-mail: mmorita{at}phealth.med.kyushu-u.ac.jp

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 ( 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. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1800–7)

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				M. Morita, L. Le Marchand, S. Kono, G. Yin, K. Toyomura, J. Nagano, T. Mizoue, R. Mibu, M. Tanaka, Y. Kakeji, et al. Genetic Polymorphisms of CYP2E1 and Risk of Colorectal Cancer: The Fukuoka Colorectal Cancer Study Cancer Epidemiol. Biomarkers Prev., January 1, 2009; 18(1): 235 - 241. [Abstract] [Full Text] [PDF]