Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan,
J Gastroenterol. 2010 Oct;45(10):1045-52. doi: 10.1007/s00535-010-0246-0. Epub 2010 Jun 12.
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.
细胞色素 P450 2C19（CYP2C19）在许多治疗药物的代谢中具有重要的临床意义。CYP2C19 有两个主要的突变点，导致其代谢能力低下。几种 CYP 酶也对化学致癌物的代谢很重要，并且有几项研究报告了 CYP 多态性与癌症易感性之间的关联。推测 CYP2C19 多态性与癌症易感性之间存在潜在关联，我们分两个阶段进行了这项研究。在第一阶段筛选了各种胃肠癌的细胞系。然后在第二阶段进行了一项临床研究，以确认与候选癌症的关联。
总共对五种胃肠癌的 114 种细胞系进行了 CYP2C19 的遗传多态性研究。基于该筛选研究提示与胆道癌有关联，我们通过招募 65 名胆道癌患者和 566 名良性疾病患者作为对照，进行了一项相关研究。
在所研究的 114 种细胞系中，胆道癌与 CYP2C19 的弱代谢者关系最密切。在 65 名胆道癌患者中，有 18 名（28%）为 CYP2C19 的弱代谢者，而 566 名对照患者中有 87 名（15%）为弱代谢者。与广泛代谢者相比，中代谢者和弱代谢者患胆道癌的风险的年龄和性别调整比值比分别为 1.5（95%CI：0.8-3.0，P=0.17）和 2.7（1.3-5.9，P=0.006）。
CYP2C19 的遗传多态性与胆道癌的易感性有关。
