EPHX 1基因多态性与原发性肝癌易感性的关系

Polymorphism of microsomal epoxide hydrolase and susceptibility to primary hepatocellular carcinoma

目的：探讨Ⅱ相代谢酶微粒体环氧化物水解酶EPHX1基因多态性和烟酒习惯及其相互作用与原发性肝癌易感性的关系。方法：采用病例-对照研究和聚合酶链式反应-限制性片段长度多态性（polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP）技术对广西地区105例原发性肝癌患者及151例健康对照者的EPHX1第3外显子113密码子基因型进行检测,并调查研究对象的烟酒习惯。结果：EPHX1第3外显子113密码子Tyr/Tyr、Tyr/His、His/His3种基因型频率在病例组分别为27.62%、21.90%、50.48%,对照组则分别为21.19%、34.44%、44.37%,2组差异无统计学意义（P〉0.05）;EPHX1第3外显子113密码子基因型为His/His的个体在吸烟因素存在时,发生肝癌的危险性增加,OR值为2.99（95%CI：1.29～6.91）;在HBV阳性的人群中,吸烟和饮酒习惯与EPHX1易感基因型对肝癌的发生有明显的协同作用。结论：EPHX1第3外显子基因多态与吸烟、饮酒等环境因素的相互作用可能增加个体患肝癌的危险性。

Objective：This study intended to explore the relationships of the polymorphism of phase Ⅱ drug-metabolizing enzyme, microsomal epoxide hydrolase 1 （EPHX 1） with the habits of smoking and alcohol drinking, and their interactions on risk of deve-loping primary hepatocellular carcinoma （HCC）. Methods： The genotypes at codon 113 of exon 3 of gene EPHX 1 were analyzed in 105 patients with HCC and 151 healthy controls in Guangxi Province by using polymerase chain reaction followed by restriction fragment length polymorphism （PCR-RFLP）. The habits of smoking and alcohol drinking of all the subjects were investigated. Results：The frequencies of Tyr/Tyr, Tyr/His and His/His genotypes at codon 113 of exon 3 of gene EPHX 1 were 27.62%, 21.90% , and 50.48% for HCC patients and 21.19%, 34.44% , and 44.37% for healthy controls, respectively. There was no significant difference （P〉0.05）. Smoking increased the risk of developing HCC for patients with His/His genotype. The OR value was 2.99 （95%CI： 1.29-6.91）. For the HBV-positive patients, polymorphism of EPHX 1 and the habits of smoking and alcohol drinking had synergistic effects on the development of HCC. Conclusion： The interaction between the environmental factors such as smoking and alcohol drinking and polymorphism of EPHX 1 gene may increase the risk of developing HCC.