ERCC2基因多态性与非吸烟人群肺癌易感性的关系

钱碧云; 周晓颖; 张寰; 张丽娜; 郑红; 俞和; 陈可欣

doi:10.3969/j.issn.1000-8179.2011.02.002

摘要: 目的：探讨在从不吸烟人群中核苷酸切除修复交叉互补（excision repair cross complementing， ERCC2）基因的单核苷酸多态性对肺癌发病的影响。方法：采用病例对照的研究方法，运用TaqMan荧光定量实时PCR分析方法对非小细胞肺癌患者和健康对照者进行ERCC2基因rs1799793和rs13181位点的基因多态性检测。按照吸烟状态进行分层分析，采用χ2检验比较各基因型在非吸烟的病例对照组中分布频率的差异；采用非条件Logistic回归模型分析基因多态性对非吸烟者患肺癌的影响；最后提取迄今为止发表的全部非吸烟人群中的ERCC2基因多态性与肺癌发病相关研究，进行Meta分析。结果：549例非小细胞肺癌患者和577例健康对照者中ERCC2基因多态性分布差异没有统计学意义。不过在非吸烟组中携带rs1799793 （Asp312Asn）变异等位基因型312A，个体患肺癌的风险是携带野生型GG的2.1倍（OR=2.10， 95% CI：1.22～3.64）；特别是患肺腺癌的风险1.2倍（OR=2.20， 95% CI：1.20～4.05）。携带rs13181 （Lys751Gln）变异等位基因型751C，调整其他危险因素后患肺癌的风险是野生型AA的1.7倍（OR=1.72， 95% CI： 1.01～2.95）。总结全世界范围发表的肺癌相关ERCC2基因研究，对非吸烟人群1 550例rs1799793位点和1 645例rs13181位点的病例对照研究数据进行分析，结果发现不论东西方人种，携带变异型ERCC2基因都将增加非吸烟肺癌的发病危险，有统计学意义。结论：携带ERCC2变异等位基因型的非吸烟人群可能是非小细胞肺癌的易感人群。

Abstract: Association between ERCC2 Gene Polymorphisms and the Risk of Lung Cancer in Non-smokersBiyun QIAN, Xiaoying ZHOU, Huan ZHANG, Lina ZHANG, Hong ZHENG, He YU, Kexin CHENCorrespondence to: Kexin CHEN , E-mail: chenkexin1963@yahoo.comDepartment of Cancer Epidemiology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Preventionand Therapy, Tianjin 300060, ChinaThis work was supported by Tianjin Natural Science Funding (No. 08JCYBJC05200) and National Natural Science Foundation of Chi-na (No. 81071914)Abstract Objective: To evaluate the influence of single nucleotide polymorphisms in ERCC2 on susceptibility to non-smalllung cancer among non-smokers. Methods: A case-control study in Tianjin was conducted. Genotypes were determined by TaqMan re-al-time PCR, and a test was used to compare the distribution of the genotypes between cases and controls in the different smoking statussubgroups. Unconditional logistic regression was used to analyze the OR and adjusted OR by covariates. Then we performed a me-ta-analysis extracted from the published data within a non-smoking population. Results: No significant differences in ERCC2 genotypedistribution were found between 549 lung cancer cases and 577 healthy controls. The results showed that in the subgroup of nonsmok-ers, the individuals with the ERCC2 312A (rs1799793) genotype had a 2.1 fold (OR = 2.10; 95%CI: 1.22-3.64) higher risk of lung can-cer, and a specific 1.2-fold increased risk of adenocarcinoma ( OR = 2.20; 95% CI: 1.20-4.05), compared to those with the 312GG geno-type. Also among the non-smokers, individuals with the ERCC2 751C (rs13181) genotype had a 1.7-fold (OR = 1.72; 95% CI:1.01-2.95) higher risk of lung cancer compared to those with the wild type genotype after adjusting for the relevant covariates. Me-ta-analyses of rs1799793 and rs13181 extracted from published data, including 1550 smokers and 1645 nonsmokers, showed that ER-CC2 variant alleles were associated with the risk of lung cancer in the Caucasian and Asian population. Conclusion: Non-smokers whohave the ERCC2 312A or ERCC2 751C allele may have a high risk of lung cancer.Keywords Lung neoplasm; Non-smokers; ERCC2 gene; Polymorphism; Meta-analysis