DNA修复基因XPCAla499Val、Lys939Gln多态与肺癌易感性  

Association of two exonic genetic polymorphisms in the DNA repair gene XPC with risk of lung cancer in Chinese population

作　　者：胡志斌[1] 王永岗[2] 马红霞[1] 谭文[2] 钮菊英[1] 林东昕[2] 沈洪兵[1] 

机构地区：[1]南京医科大学公共卫生学院流行病与卫生统计系,210029 [2]中国医学科学院协和医科大学肿瘤研究所肿瘤医院病因及癌变研究室

出　　处：《中华医学遗传学杂志》2005年第4期415-418,共4页Chinese Journal of Medical Genetics

基　　金：国家"973"重大基础研究项目(2002CB512902)~~

摘　　要：目的探讨中国人DNA修复基因XPCAla499Val、Lys939Gln多态与肺癌易感性的关系。方法以社区为基础的病例对照研究。经组织学确诊的肺癌病例320例,相同地区年龄和性别频数匹配的人群对照322人,以PCR为基础的方法进行多态性检测,比较不同基因型与肺癌风险的关系,并探讨吸烟在其中的影响。结果与携带499Ala/Ala基因型者比较,携带至少1个499Val等位基因者(即Ala/Val和Val/Val基因型)肺癌风险增加1.54倍(95%CI=1.11～2.14),而同时有499和939两个位点变异等位基因者肺癌风险增加2.55倍(95%CI=1.45～4.52)。交互作用分析显示,XPC499Val变异基因型与吸烟具有超相乘模型的交互作用,同时有两个位点变异等位基因并吸烟者肺癌风险增加可高达7.36倍(95%CI=3.19～17.0)。结论XPCAla499Val和Lys939Gln多态可能与中国汉族人群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 relationship between two exonic polymorphisms of DNA repair gene XPC and the susceptibility to lung cancer. Methods Genotypes were determined by the primer introduced restriction analysisPCR（PIRA-PCR） and the PCR-restriction fragment length polymorphism（PCR-RFLP） approaches, respectively, in 320 histologically-confirmed lung cancer cases and 322 age and sex frequency-matched caneer-free controls. Results Multivariate logistic regression analysis revealed that individuals carrying at least one 499Val variant allele （Ala/Val ＋ Val/Val genotypes） had a significantly increased risk for lung cancer （adjusted OR = 1.54; 95%CI： 1.11-2.14）, compared with the wild-type genotype （499Ma/Ma）. Furthermore, individuals with both putative risk genotypes had a significantly higher risk （adjusted OR=2.55; 95%CI： 1.45-4.52）, compared with those with both wild-genotypes. In addition, a potential super multiplicative gene-environment interaction between Ma499Val genotypes and smoking on lung cancer risk was unveiled. The odds ratios of lung cancer for individuals with both putative risk genotypes were 2.63 （95%CI = 1.23-5.62） in nonsmokers and 7.36 （95%CI = 3.19-17.0） in smokers, respectively. Conclusion These findings support the hypothesis that these two XPC variants may contribute to the risk of developing lung cancer.

关 键 词：DNA修复基因 XPC Ala499Val Lys939Gln 基因多态性 肺癌 易感性 

分 类 号：R734.2[医药卫生—肿瘤] R394[医药卫生—临床医学]