ERCC1、XRCC1单核苷酸多态性与非小细胞肺癌铂类药物化疗预后关系的研究  

Polymorphisms of ERCC1,XRCC1 and its association with survival to platin-based chemotherapy in advanced non-small cell lung cancer

作　　者：成红艳[1] 陈宝安[1] 孙新臣[2] 邓雨霞[1] 孙宁[3] 曹远东[1] 

机构地区：[1]东南大学附属中大医院肿瘤科,江苏南京210009 [2]江苏省人民医院放疗科,江苏南京2100068 [3]江苏省肿瘤医院肿瘤科,江苏南京210006

出　　处：《东南大学学报（医学版）》2011年第5期717-721,共5页Journal of Southeast University(Medical Science Edition)

基　　金：江苏省自然科学基金前期预研项目(BK2005203);南京市医学科技发展重点项目基金(ZKX05030)

摘　　要：目的:探讨核苷酸切除修复交叉互补组基因1(ERCC1)、人类X射线交错互补修复基因1(XRCC1)单核苷酸多态性(SNP)与非小细胞肺癌(NSCLC)铂类药物化疗后的预后关系。方法:经病理学确诊的晚期NSCLC患者120例,采用铂类为主的两药联合化疗方案,化疗前采集患者的外周血。采用基因芯片法检测ERCC1(118)、XRCC1(399)的SNP,并随机抽取10%的样本进行基因测序来验证该方法的准确性。比较不同基因型与铂类药物化疗后生存期的关系。结果:成功进行基因分型,野生型、杂合型和突变型的叠加荧光分别显示为绿色、黄色和红色,与基因测序结果完全吻合。中位随访时间11个月(6～49个月)。携带ERCC1(118)C/C、C/T+T/T基因型患者铂类化疗后中位生存时间(MST)、1年生存率、2年生存率及3年生存率分别为10.9个月、35.9%、6.3%、1.6%和13.5个月、59.5%、19.0%、14.3%,两组间比较差异均有统计学意义(P<0.05);携带XRCC1(399)G/G基因型、G/A+A/A基因型MST、1年生存率、2年生存率、3年生存率分别为15.2个月、59.1%、15.9%、6.8%和11.1个月、35.5%、8.1%、6.5%,两组间比较差异均有统计学意义(P<0.05)。结论:ERCC1、XRCC1基因多态性与NSCLC患者铂类药物化疗后的生存期有显著相关性,有可能成为铂类药物化疗后生存期的预测指标。Objective： To investigate the relationship between genetic polymorphisms of ERCC1,XRCC1 and survival of patients with advanced non-small cell lung cancer（NSCLC） treated with platinum based chemotherapy.Methods： A total of 120 patients with advanced NSCLC were routinely treated by cisplatin or carboplatin based chemotherapy.The polymorphic genotypes were analyzed by gene-chip method using DNA samples isolated from peripheral blood before treatment.Besides,10% samples were extracted randomly for sequencing to test the accuracy of this method.To explored the association between SNP of ERCC1（118）,XRCC1（399） and prognosis to platinum-based chemotherapy in advanced NSCLC patients.Results： Homozygous wild type,heterozygote type and homozygous mutant type yielded green,yellow and red fluorescence,respectively.The results were according to gene sequencing.Median follow-up period was 11 months.MST,1-year survival,2-year survival and 3-year survival rates of patients with the ERCC1（118）C/C genotype,C/T＋T/T genotype were 10.9 months,35.9%,6.3% and 1.6% vs 13.5 months,59.5%,19.0% and 14.3% respectively,with significant difference（P0.05）.MST and 1-year survival,2-year survival and 3-year survival rates of patients with the XRCC1（399） G/G genotype and G/A＋A/A genotype were 15.2 months and 59.1%,15.9%,6.8% vs 11.1 months,35.5%,8.1%,6.5% respectively,with significant difference（P0.05）.Conclusion： Polymorphisms of ERCC1,XRCC1 might be associated with overall survival period in patients with advanced NSCLC after treatment with platin-based chemotherapy,which might be the predictive markers for overall survival.

关 键 词：单核苷酸多态性 基因芯片 基因型 非小细胞肺癌 抗肿瘤联合化疗方案 生存期 

分 类 号：R734.2[医药卫生—肿瘤]