title: Genetic polymorphism in cytochrome P450 7A1 and risk of colorectal cancer: the Fukuoka Colorectal Cancer Study.
abstract: Bile acids have long been implicated in the etiology of colorectal cancer, but epidemiologic evidence remains elusive. Cholesterol 7alpha-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.
authors.affiliation: Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan. thagi@med.kyushu-u.ac.jp
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hagiwara
authors.forename: Suminori
authors.initials: S
authors.lastname: Kono
authors.forename: Guang
authors.initials: G
authors.lastname: Yin
authors.forename: Kengo
authors.initials: K
authors.lastname: Toyomura
authors.forename: Jun
authors.initials: J
authors.lastname: Nagano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizoue
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Mibu
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okamura
authors.forename: Kouji
authors.initials: K
authors.lastname: Ikejiri
authors.forename: Kitaroh
authors.initials: K
authors.lastname: Futami
authors.forename: Youichi
authors.initials: Y
authors.lastname: Yasunami
authors.forename: Takafumi
authors.initials: T
authors.lastname: Maekawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Takenaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichimiya
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Imaizumi
mesh_terms: D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000378:metabolism; D016022:Case-Control Studies; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D001647:Bile Acids and Salts; D002790:Cholesterol 7-alpha-Hydroxylase