Introduction: 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.
Methods: Subjects were 96 cases of proximal colon cancer, 357 of distal colon/rectal cancer and 961 age‐ and sex‐matched non‐cancer controls. We examined five loci, including rs3808607, by TaqMan method. Impact of each locus or haplotype were evaluated according to subsite by polytomous logistic regression models adjusted for potential confounders including age, sex, regular exercise, family history of colorectal cancer, body mass index, drinking habit and folate consumption.
Results: In locus‐specific analyses, we saw no association with rs3808607 for any subsite. Rs11786580 showed a statistically significant positive association with proximal colon cancer, while association was not seen in distal colon and rectal cancer. 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. Conclusion: 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.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B116.