DNA损伤结合蛋白2基因单核苷酸多态性相关的肺癌发病风险模型

Model of Lung Cancer Risk with Single Nucleotide Polymorphism in the DNA Damage Binding Protein 2

[目的]研究DNA损伤结合蛋白2基因(DDB2基因)单核苷酸多态性位点rs3781620等位基因(nt23314 C>G)多态与肺癌易感性的关系,并建立环境-遗传因素的肺癌发病风险模型。[方法]运用病例-对照研究,选择湖北省各地区医院经病理诊断确诊的原发性肺癌患者216例为病例组.社区人群448人为对照组,以Taqman探针基因分型的方法进行基因分型,采用多因素非条件Logistic回归后退法筛选肺癌相关危险因素并计算人群归因危险度百分比,绘制受试者工作特征曲线(ROC)。[结果]社区对照人群中DDB2基因的C和G两种等位基因分布频率分别为66.6%和33.4%。多因素分析结果表明与携带DDB2基因单核苷酸多态性位点rs3781620等位基因的野生型纯合子CC基因型者相比.携带CG或GG基因型的研究对象患肺癌危险度为OR=1.634(95%CI:1.104～2.420);年长者(>60岁)发生肺癌的危险度为OR=1.641(95%Cl:1.110～2.426);一级亲属家族有肿瘤史的危险度为OR=2.972(95%Cl:1.452～6.084);轻度和重度吸烟者分别为OR=1.649(95%CI:0.962～2.826)、OR=6.351(95%CI:3.978～10.139);饮酒为OR=1.559(95%CI:1.034～2.349);体育锻炼为OR=0.568(95%CI:0.383～0.844)。以上各因素的人群归因危险度百分比分别为11.27%、13.34%、7.16%、9.67%、44.90%、8.71%和-11.67%。Logistic回归模型ROC曲线下面积为0.786(95%CI:0.748～0.823)。[结论]遗传和环境因素在肺癌发病中起作用:一级亲属肿瘤家族史、DDB2基因单核苷酸多态性位点rs3781620 CG或GG基因型与肺癌易感性有关;不良的生活方式(吸烟、饮酒和缺乏锻炼)可增加肺癌的危险性。该模型对肺癌发病风险的评估能力中等。

[ Objective ] To explore the association between polymorphisms of DNA damage binding protein 2（ DDB2 ）gene and lung cancer risk. To assess the risk of lung caner by building prediction model of gene-environment factors. [ Methods ] The results were analyzed by multivariate uncondictional logistic regression, and polymorphisms rs3781620 were genetyped by a polymerase chain reaction（ PCR ）-based fluorescence 5＇-nuclease（ TaqMan ）assay in 216 histologically confirmed lung cancer cases and 448 cancer free controls. [ Results ] It was found that individuals, compared with carrying CC genetype, carrying CG/GG genetypes had a significantly increased risk for lung cancer （ OR=1.634, 95%CI： 1.104-2.420 ）. Older individuals （OR=1.641, 95%CI： 1.110-2.426 ）, family history of cancer in immediate relatives （OR=2.972, 95%CI： 1.452-6.084 ）, light smoking（ 1-29 pack-years ）（ OR=1.649, 95%CI： 0.962-2.826 ）, heavy smoking（ 〉29 pack-years ） （OR=6.351, 95%CI： 3.978-10.139 ）, and drinking status（ OR=1.559, 95%CI： 1.034-2.349 ）were risk factors, whereas exercise（ OR=0.568, 95%CI： 0.383-0.844）was protective factor. Population Attributable Risk Proportions of these factors were 11.27%, 13.34%, 7.16%, 9.67%, 44.90%, 8.71%, and -11.67% respectively. The ROC curve area of logistic regression model was 0.786（ 95%CI： 0.748-0.823 ）. [ Conclusion ] The model including six factors has better capability for lung cancer risk evaluation.