This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hagiwara, T. Articles by Imaizumi, N. Search for Related Content PubMed PubMed Citation Articles by Hagiwara, T. Articles by Imaizumi, N.

Genetic Polymorphism in Cytochrome P450 7A1 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, Maidashi, Higashi-ku, Fukuoka; ⁴ Department of Gastroenterological Surgery, National Kyushu Cancer Center, Notame, Minami-ku, Fukuoka; ⁵ Division of Surgery, National Kyushu Medical Center, Jigyohama, Chuo-ku, Fukuoka; ⁶ Department of Surgery, Fukuoka University Chikushi Hospital, Oaza-zokumyoin, Chikushimo-shi; ⁷ The First and ⁸ Second Departments of Surgery, Fukuoka University School of Medicine, Nanakuma, Jonan-ku, Fukuoka; ⁹ Division of Surgery, Fukuoka City Hospital, Yoshizuka-honmachi, Hakata-ku, Fukuoka; ¹⁰ Division of Surgery, Hamanomachi General Hospital, Maizuru, Chuo-ku, Fukuoka; and ¹¹ Division of Surgery, Fukuoka Red Cross Hospital, Ogusu, Minami-ku, Fukuoka, Japan

Requests for reprints: Tomoko Hagiwara, Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Phone: 81-92-642-6112; E-mail: thagi{at}med.kyushu-u.ac.jp.

Bile acids have long been implicated in the etiology of colorectal cancer, but epidemiologic evidence remains elusive. Cholesterol 7-hydroxylase (CYP7A1) is the rate-limiting enzyme in the synthesis of bile acids from cholesterol in the liver, and thus may be an important determinant of bile acid production. We examined the association between the CYP7A1 A-203C polymorphism and colorectal cancer. The CYP7A1 A-203C polymorphism was determined by the PCR-RFLP method in 685 incident cases of colorectal cancer and 778 controls randomly selected from a community in the Fukuoka area, Japan. The CC genotype was slightly less frequent in the case group, and the adjusted odds ratio for the CC versus AA genotype was 0.88 (95% confidence interval, 0.65-1.20). In the analysis by subsite of the colorectum, a decreased risk associated with the CYP7A1 CC genotype was observed for proximal colon cancer, but not for either distal colon or rectal cancer. The adjusted odds ratios (95% confidence intervals) of proximal colon cancer for the CC genotype were 0.63 (0.36-1.10) compared with the AA genotype, and 0.59 (0.37-0.96) compared with the AA and AC genotypes combined. A decreased risk of proximal colon cancer in relation to the CC genotype of CYP7A1 A-203C, which probably renders less activity of the enzyme converting cholesterol to bile acids, is new evidence for the role of bile acids in colorectal carcinogenesis.

Key Words: colorectal cancer • CYP7A1 • bile acids • case-control study