title: Association between CYP7A1 and the risk of proximal colon cancer in Japanese.
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.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Satoyo
authors.initials: S
authors.lastname: Hosono
authors.forename: Miki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Takakazu
authors.initials: T
authors.lastname: Kawase
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirai
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima