COX-2基因启动子区单核苷酸多态与肝癌遗传易感性的关系

摘要

Objective To evaluate the effects of SNPs in the promoter of COX-2 gene on the risk of developing hepatocellular carcinoma. Methods Genotypes of 270 cases of hepatocellular carci-noma and 640 control subjects were determined by polymerase chain reaction-based restriction frag-ment length polymorphism (PCR-RFLP). The samples of DNA were extracted from the peripheral blood of all subjects. All patients with hepatocellular carcinoma were diagnosed by pathological or cy-tological examination. Ors and 96% CI were calculated by logistic regression to explore the associa-tion between different genotypes or haplotypes and the risk of hepatocellular carcinoma. Results Three SNPs, -1290A＞G, -1195G＞A and -765G＞C were identified. A case-control analysis re-vealed 1.57-fold (95% CI=1.01-2.44) and 2.89-fold (95% CI=1.65-5.08) excess risks of develo-ping hepatocellular carcinoma for the -1195AA or -765CG genotype carriers compared with noncar-riers, respectively. Compared with A-1290-G-1195-G-765 containing haplotype,greater risks of develo-ping hepatocellular carcinoma were observed for A1290-A-1195-G-765 (OR= 1.27; 95% CI= 1.01 -1.60) and A-1290-A-1195-C-765(OR= 7.95; 95% CI= 1.76-36.02) containing haplotypes. A greater risk of developing hepatoeellular carcinoma was observed for A-1195and C-765 containing haplotype compared with other haplotypes, suggesting an interaction between the -1195A and -765C in the context of haplotype. Conclusion The SNP of -1195A＞G and -765G＞C in the COX-2 promoter may play an important role in mediating hereditary susceptibility to developing hepatocellular carcinoma.%目的 探讨COX-2基因启动子区的单核苷酸多态与肝癌发生风险的关系.方法 研究对象包括270例肝癌病人和540例正常对照.采用PCR-限制性片段长度多态方法 进行COX-2基因启动子区-1290A＞G,-1195G＞A和-765G＞C多态的基因型分析,不同基因型与单体型携带者发生肝癌的相对风险度的评估使用比值比(OR)及95%可信区间(CI).结果 多变量logistic回归分析显示-1195AA和-765GC基因型与肝癌风险增高相关,OR值分别为1.57(95%CI=1.01～2.44)和2.89(95%CI=1.65～5.08).单体型分析显示:与A_1290-G-1195-G_765相比较,含有-1195A等位基因的A-1290-A-1195-G-765和A-1290-A-1195-C-765两种单体型发生肝癌的相对风险增高,OR值分别为1.27(95%CI=1.01～1.60)和7.95(95%CI=1.76～36.02).同时包含-1195A等位基因和-765C等位基因的单体型发生肝癌的OR值较高.结论 COX-2基因启动子区的-1195G＞A和-765G＞C单核苷酸多态与肝癌遗传易感性相关.