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Genetic Polymorphisms of CYP2E1 and Risk of Colorectal Cancer: The Fukuoka Colorectal Cancer Study

Departments of ¹ Preventive Medicine, ² Surgery and Oncology, and ³ Surgery and Science, Graduate School of Medical Sciences, Kyushu University; ⁴ Department of Gastroenterological Surgery, National Kyushu Cancer Center; ⁵ Division of Surgery, National Kyushu Medical Center; ⁶ Department of Surgery, Fukuoka University Chikushi Hospital; ⁷ Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University; ⁸ Division of Surgery, Fukuoka City Hospital; ⁹ Division of Surgery, Hamanomachi General Hospital; ¹⁰ Division of Surgery, Fukuoka Red Cross Hospital, Fukuoka, Japan and ¹¹ Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii

Requests for reprints: Makiko Morita, Department of Molecular Biology, University of Occupational and Environmental Health, Japan, Yahatanishi-ku, Kitakyushu 807-8555, Japan. Phone: 81-93-691-7423; Fax: 81-93-692-2766. E-mail: mmorita{at}med.uoeh-u.ac.jp

Cytochrome P450 2E1 (CYP2E1) is involved in the metabolic activation of a wide variety of potential carcinogens, and functional polymorphisms in the CYP2E1 gene have been investigated in relation to colorectal cancer. We examined the relation of the CYP2E1 RsaI and 96-bp insertion polymorphisms to colorectal cancer risk and the interaction between these polymorphisms and some lifestyle risk factors. Subjects were 685 incident cases of colorectal cancer and 778 community controls. Statistical adjustment was made for alcohol use, body mass index, physical activity, and other factors. The RsaI c2 allele was associated with a decreased risk of rectal cancer [adjusted odds ratio for at least one c2 allele, 0.71; 95% confidence interval (95% CI), 0.53-0.95], and an increased risk of rectal cancer was observed among individuals having one or two 96-bp insertion alleles (adjusted odds ratio, 1.40; 95% CI, 1.06-1.85). Individuals with two 96-bp insertion alleles showed a 2.28-fold increase in colon cancer risk (95% CI, 1.29-4.01). The two polymorphisms were in almost complete linkage disequilibrium (D' = 0.94). A positive association between alcohol intake and colorectal cancer was observed only in individuals without RsaI c2 allele (P_trend = 0.03) or in those without 96-bp insertion allele (P_trend = 0.009). Colon cancer risk was increased in relation to red meat intake only in individuals having one or two 96-bp insertion alleles (P_interaction = 0.03). The present study suggests that variation in activity and inducibility of CYP2E1, in relation to alcohol or red meat intake, contributes to the development of colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(1):235–41)