DNA损伤结合蛋白(DDB2)基因单核苷酸多态性与肺癌易感性研究  

Association of genetic polymorphisms in the DNA repair gene DDB2 with risk of lung cancer

作　　者：吕美霞[1] 杨晓波[1] 白云[1] 何越峰[1] 施侣元[2] 邬堂春[1] 

机构地区：[1]华中科技大学同济医学院公共卫生学院职业医学研究所,环境与健康教育部重点实验室,湖北武汉430030 [2]华中科技大学同济医学院公共卫生学院流行病与卫生统计学系,湖北武汉430030

出　　处：《疾病控制杂志》2007年第5期444-447,共4页Chinese Journal of Disease Control and Prevention

基　　金：国家自然科学基金青年基金(3050416);国家科技部重大基础研究和发展项目(2002CB512905)

摘　　要：目的探讨DNA修复基因(DDB2)单核苷酸多态位点rs830083C>G变异与肺癌易感性的关系。方法采用病例对照研究,选取湖北省各地区医院经病理诊断确诊的原发性肺癌406例,社区对照人群478例为研究对象,以Taqman探针进行基因分型,采用多因素非条件logistic回归调整年龄、性别、吸烟、一级亲属家族肿瘤史,比较不同基因型与肺癌危险的关系,并探讨吸烟与基因的交互作用。结果与携带野生型纯合子CC基因型者相比,携带CG杂合子者肺癌风险增加0.49倍,而携带GG变异纯合子者肺癌发生风险增加0.72倍,呈剂量-效应关系。有一个C>G变异的个体,累计吸烟量与肺癌发生危险度呈剂量-效应关系。交互作用分析显示,吸烟暴露与DDB2基因rs830083多态存在交互作用,同时存在高暴露累计吸烟量和杂合子CG基因型或变异纯合子GG基因型的个体肺癌发病危险度分别为5.99和2.89;吸烟与rs830083位点变异两因素同时存在时对肺癌发生的危险远大于两因素单独存在时对肺癌发生危险的影响。结论DDB2基因SNP位点rs830083C>G变异可能与肺癌遗传易感性有关,并可显著增加吸烟对肺癌的危险性。　Objective To explore the association between polymorphisms of DNA damage binding protein 2（DDB2）gene and lung cancer risk.Methods The results were analyzed by multivariate uncondictional logistic regression,and polymorphisms rs830083 were Genetyped by a polymerase chain reaction（PCR）-based fluorescence 5＇-nuclease（TaqMan）assay in 406 histologically confined lung cancer cases and 478 cancer free controls.Results It was found that individuals carrying CG Genetypes,compared with those carrying CC genetype,had a significantly increased risk for lung cancer（adjusted OR=1.49）,and 1.72 fold risk for individuals carrying GG genetype.There was a dose-effect relationship between the number of variants and lung cancer risk.With the increasing of cumulative tobacco consumption,the risk of lung cancer were increased for individuals carrying CG genotypes.Gene-environment interaction in lung cancer risk was observed.There was increased risk for individuals carrying CG/GG genotypes and heavy smoking,the adjust OR being 5.99 and 2.89,respectively.Furthermore,a potential super multiplicative gene-environment interaction was observed between DDB2 polymorphisms and cumulative tobacco consumption with lung cancer risk.Conclusions These findings support the hypothesis that polymorphisms of DDB2 gene may contribute to the risk of lung cancer.

关 键 词：多态性 单核苷酸 肺肿瘤 疾病易感性 

分 类 号：R734.2[医药卫生—肿瘤]