A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer
A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer
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DOI：
10.1007/s00535-010-0246-0
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发表时间：
2010-10-01
影响因子：
6.3
通讯作者：
Koike, Kazuhiko
中科院分区：
文献类型：
--
作者：
Isomura, Yoshihiro;Yamaji, Yutaka;Koike, Kazuhiko
细胞色素P450 2C 19（CYP 2C 19）对许多治疗药物的代谢具有重要的临床意义。CYP 2C 19有两个主要的点突变位点，导致代谢能力降低。几种β-淀粉酶对化学致癌物的代谢也很重要，几项研究报道了β-淀粉酶多态性与癌症易感性之间的关系。推测CYP 2C 19多态性与癌症易感性之间的潜在关联，我们分两个阶段进行了这项研究。在第一阶段筛选各种胃肠癌的细胞系。在第二阶段的临床研究中，我们对5种胃肠道肿瘤的114个细胞系进行了CYP 2C 19基因多态性的研究。在此基础上，我们进行了一项相关研究，招募了65例胆道癌患者和566例良性疾病患者作为对照，在研究的114种细胞系中，胆道癌与CYP 2C 19的弱代谢型相关性最强。在65例胆道癌患者中，18例（28%）为CYP 2C 19的弱代谢型，而566例对照患者中87例（15%）为弱代谢型。与快代谢型相比，中代谢型和慢代谢型患者胆道癌风险的年龄和性别校正比值比分别为1.5（95%CI：0.8-3.0，P = 0.17）和2.7（1.3-5.9，P = 0.006）。CYP 2C 19基因多态性与胆道癌易感性相关。
Cytochrome P450 2C19 (CYP2C19) is clinically important for the metabolism of many therapeutic drugs. CYP2C19 has two main point mutation sites leading to low metabolic capacity. Several CYP enzymes are also important for the metabolism of chemical carcinogens, and several studies have reported associations between CYP polymorphism and cancer susceptibility. Speculating on a potential association between CYP2C19 polymorphism and cancer susceptibility, we conducted this study in two phases. Cell lines of various gastroenterological cancers were screened in the first phase. A clinical investigation was then conducted to confirm the association with the candidate cancer in the second phase.Genetic polymorphism of CYP2C19 was investigated in a total of 114 cell lines of five gastroenterological cancers. Based on this screening investigation suggesting an association with biliary tract cancer, we conducted a related study by recruiting 65 patients with biliary tract cancer and 566 patients with benign diseases as controls.Among the 114 cell lines investigated, biliary tract cancer was suggested to be most strongly associated with poor metabolizers of CYP2C19. Among 65 patients with biliary tract cancer, 18 (28%) were poor metabolizers of CYP2C19, whereas 87 (15%) of 566 control patients were poor metabolizers. The age- and gender-adjusted odds ratios for intermediate and poor metabolizers regarding the risk of biliary tract cancer were 1.5 (95% CI: 0.8-3.0, P = 0.17) and 2.7 (1.3-5.9, P = 0.006) compared to extensive metabolizers.A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer.