脂氧酶12编码区遗传变异与肝癌发病风险的关系

Association of genetic variant in 12-lipoxygenase and risk of hepatic carcinoma

目的 探讨脂氧酶12（LOX12）基因编码区Arg261 Gln单核苷酸多态与肝癌发病风险的相关关系.方法 采用病例对照研究策略,以PCR-限制性片段长度多态性（RFLP）方法,检测2008年1月至2012年12月在河北联合大学附属医院经病理确诊的280例肝癌患者（肝癌组）和560名健康对照个体（对照组）的LOX12基因的Arg261 Gln位点的基因型,以比值比（OR）及其95％可信区间（CI）比较各基因型与肝癌发病风险的相关关系.结果 肝癌组LOX12 261Gln等位基因频率显著高于对照组（0.563比0.437）.对照组中LOX12 Arg/Arg、Arg/Gln和Gln/Gln 3种基因型分别占24.3％（136/560）、52.9％ （296/560）和22.8％（128/560）,而肝癌组这3种基因型分别占19.1％（53/278）、49.3％（137/278）和31.6％ （88/278）,Logistic回归分析表明,与261 Arg/Arg基因型携带者相比,261Gln/Gln基因型携带者发生肝癌的风险显著增加（OR=1.83,95％CI：1.18 ～2.84,P=0.007）.吸烟分层分析显示,Arg261 Gln变异对肝癌的致病作用只存在于吸烟人群中,携带261 Gln/Gln基因型个体发生肝癌的风险比261Arg/Arg基因型携带者显著高（OR=2.23,95％ CI：1.16～4.26,P=0.020）.结论 LOX12编码区Arg261 Gln遗传变异是肝癌易感性的重要遗传因素.

Objective To explore the association of 12-lipoxygenase （LOX12） Arg261Gln polymorphism with the risk of hepatic carcinoma in Chinese population.Methods A total of 280 cases of hepatic carcinoma and 560 frequency-matched controls were recruited from January 2008 to December 2012 at Hebei United University Affiliated Hospital.The method of PCR-restriction fragment length polymorphism （RFLP） was employed to genotype LOX12 Arg261Gln polymorphism.And odds ratios （OR） and 95% confidence intervals （CI） were calculated with a model of unconditional Logistic regression.Results The alleleic frequency for LOX12 Arg261Gln was significantly higher in hepatic carcinoma cases than that in controls （0.563 vs 0.437）.For the control group,the three genotypes of LOX1 2 Arg/Arg,Arg/Gln and Gln/ Gln were 24.3% （136/560）,52.9% （296/560） and 22.8% （128/560） respectively.For the hepatic carcinoma group,these three genotypes were 19.1% （53/278）,49.3% （137/278） and 31.6% （88/278） respectively.Logistic regression analysis showed that,compared with 261 Arg/Arg genotype carriers,the subjects with 261Gln/Gln had increased risks for hepatic carcinoma （OR =1.83,95% CI：1.18-2.84）.When stratified by smoking status,the 261Gln/Gln carriers had an increased risk of developing hepatic carcinoma （OR =2.23,95% CI：1.16-4.26） among smokers,but not among non-smokers.Conclusion LOX12 Arg261Gln polymorphism is associated with the susceptibility to hepatic carcinoma.