Yao Le, Wang Hong-Cheng, Liu Jia-Zhe, Xiong Zhao-Ming
Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 310000, People's Republic of China.
Tumour Biol. 2013 Oct;34(5):3083-91. doi: 10.1007/s13277-013-0875-z. Epub 2013 Jun 12.
Cytochrome P450 (CYP) 2C19 metabolizes many promutagens and procarcinogens to biologically active metabolites, which strongly promote proliferation of cancer cells in vitro and in vivo. The CYP2C19 gene exhibits several genetic polymorphisms that are thought to play a major role in inter-individual variability in drug response, drug-xenobiotic interactions, and in cancer susceptibility. Two polymorphisms of the CYP2C19 gene (CYP2C192, CYP2C193) which was associated with reduced enzyme activity have been investigated extensively digestive tract cancer; however, these studies have yielded contradictory results. To clarify this inconsistency, we performed this meta-analysis including 15 case-control studies with a total of 3,252 cases and 6,269 controls. Overall, we found significant association between CYP2C192 and digestive tract cancer (OR = 1.27, 95 % CI, 1.07-1.51, P = 0.007) while no significant results were found for CYP2C193. Potential sources of heterogeneity including cancer types, ethnicity, source of control, and sample size of study were assessed. In the subgroup analyses by cancer types, significant association was detected only in esophagus cancer for CYP2C192. When stratified by ethnicity, significantly increased risks were found for the CYP2C192 polymorphism among Asians. This meta-analysis demonstrated that the CYP2C19*2 polymorphism is a risk factor for developing digestive tract cancer. However, additional very large-scale studies are warranted to provide conclusive evidence on the effects of the CYP2C19 gene on risk of digestive tract cancer.
细胞色素P450（CYP）2C19可将许多前诱变剂和前致癌物代谢为具有生物活性的代谢产物，这些代谢产物在体外和体内均能强烈促进癌细胞增殖。CYP2C19基因存在多种遗传多态性，这些多态性被认为在个体间药物反应差异、药物-外源性物质相互作用以及癌症易感性方面发挥着重要作用。CYP2C19基因的两种多态性（CYP2C192、CYP2C193）与酶活性降低相关，已在消化道癌方面进行了广泛研究；然而，这些研究结果相互矛盾。为了阐明这种不一致性，我们进行了这项荟萃分析，纳入了15项病例对照研究，共3252例病例和6269例对照。总体而言，我们发现CYP2C192与消化道癌之间存在显著关联（比值比=1.27，95%置信区间，1.07-1.51，P=0.007），而CYP2C193未发现显著结果。评估了包括癌症类型、种族、对照来源和研究样本量在内的潜在异质性来源。在按癌症类型进行的亚组分析中，仅在食管癌中检测到CYP2C192的显著关联。按种族分层时，亚洲人中CYP2C192多态性的风险显著增加。这项荟萃分析表明，CYP2C19*2多态性是消化道癌发生的一个危险因素。然而，需要更多非常大规模的研究来提供关于CYP2C19基因对消化道癌风险影响的确凿证据。
