Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi, Department of Epidemiology, Nagoya University Graduate School of Medicine, Aichi, Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Science, Aichi, Department of Gastroenterological Surgery, Department of Pathology and Molecular Diagnosis, Aichi Cancer Center Hospital, Aichi, Director, Aichi Cancer Center Research Institute, Aichi
Received September 18, 2009; accepted September 29, 2009; available online October , 2009
Abstract: Bile acids have long been implicated in the etiology of colorectal carcinogenesis by their genotoxicity as well as cytotoxicity. Cholesterol 7-alfa-hydroxylase (CYP7A1) is the rate-limiting enzyme that converts cholesterol into cholesterol 7-alfa-hydroxycholesterol in the first step of the classical pathway of bile acid synthesis. Recently, an association between a polymorphism (-204A>C, rs3808607) in CYP7A1 and proximal colon cancer/adenoma has been reported, which was not observed with distal colon or rectal cancer/adenoma. In this case-control study, we examined the association between haplotypes of CYP7A1 and proximal or distal colon/rectal cancer risk in a Japanese population. Subjects were 96 cases of proximal colon cancer, 357 of distal colon/rectal cancer and 961 age- and sex-matched non-cancer controls at Aichi Cancer Center. We examined five loci, including rs3808607, and evaluated the impact of haplotype on risk. In locus-specific analyses, we saw no association with rs3808607 for any site. Haplotype analyses revealed that the TAAGG haplotype was positively associated with proximal colon cancer [confounder-adjusted odds ratio: 1.72 (95% confidence interval: 1.10-2.71), p=0.018] but not with distal colon and rectal cancer combined. This association was consistently observed in analyses stratified by potential confounders. Our results indicate that CYP7A1 plays a role in the carcinogenesis of colorectal cancer specifically in the proximal colon. Confirmation of this association in other epidemiologic studies and biological evaluation of the TAAGG haplotype are warranted.(IJMEG909001).
Key words: CYP7A1, polymorphisms, proximal colon cancer, Japanese
Address all correspondence to: Keitaro Matsuo, MD Division of Epidemiology and Prevention Aichi Cancer Center Research Institute 1-1 Kanokoden, Chikusa-ku Nagoya 464-8681, Japan. Tel: +81-52-762-6111; Fax: +81 52 763 5233 E-mail: email@example.com.