Genetic polymorphism in cytochrome P450 7A1 and risk of colorectal cancer: The Fukuoka colorectal cancer study
Genetic polymorphism in cytochrome P450 7A1 and risk of colorectal cancer: The Fukuoka colorectal cancer study
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DOI：
10.1158/0008-5472.can-04-3872
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发表时间：
2005-04-01
期刊：
影响因子：
11.2
通讯作者：
Imaizumi, N
中科院分区：
文献类型：
--
作者：
Hagiwara, T;Kono, S;Imaizumi, N
长期以来，胆汁酸一直与结直肠癌的病因有关，但流行病学证据仍然难以捉摸。胆固醇7 α-羟化酶（CYP 7A 1）是肝脏中胆固醇合成胆汁酸的限速酶，因此可能是胆汁酸产生的重要决定因素。我们研究了CYP 7A 1 A-203 C多态性与结直肠癌之间的关联。采用PCR-RFLP方法对日本福冈地区685例大肠癌患者和778例对照者的CYP 7A 1 A-203 C多态性进行了检测。CC基因型在病例组中的频率略低，CC与AA基因型的校正比值比为0.88（95%置信区间，0.65-1.20）。在结直肠亚位点分析中，观察到与CYP 7A 1 CC基因型相关的近端结肠癌风险降低，但远端结肠癌或直肠癌风险未降低。CC基因型与AA基因型相比，近端结肠癌的校正比值比（95%置信区间）为0.63（0.36-1.10），与AA和AC基因型组合相比为0.59（0.37-0.96）。与CYP 7A 1A-203 C的CC基因型相关的近端结肠癌的风险降低，这可能使得将胆固醇转化为胆汁酸的酶的活性降低，这是胆汁酸在结肠直肠癌发生中的作用的新证据。
Bile acids have long been implicated in the etiology of colorectal cancer, but epidemiologic evidence remains elusive. Cholesterol 7 alpha-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.