XRCC1单核苷酸多态性对非小细胞肺癌患者顺铂疗效的影响  

Effects of genetic polymorphisms of XRCC1 on the efficacy of platinum-based chemotherapy for advanced nonsmall cell lung cancer

作　　者：周国仁[1] 蒋鸣[2] 叶劲军[2] 冯继锋[1] 陆建伟[1] 蒋春莲[3] 

机构地区：[1]江苏省肿瘤医院肿瘤内科,江苏省南京市210009 [2]江苏省肿瘤医院肿瘤放疗科,江苏省南京市210009 [3]南京医科大学附属南京医院病理科,江苏省南京市210006

出　　处：《实用老年医学》2013年第11期897-899,907,共4页Practical Geriatrics

基　　金：江苏省卫生厅科研项目(P200910)

摘　　要：目的探讨人类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)铂类药物化疗后预后的关系。方法采用MALDI-TOF-MS法检测204例经病理学确诊的接受铂类药物化疗的晚期NSCLC患者XRCC1(399)的基因型,并随机抽取5%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 204例NSCLC患者中,部分缓解61例,疾病稳定116例,疾病进展27例;治疗有效率为29.9%,无效率为70.1%。携带XRCC1(399)G/G、G/A+A/A基因型的NSCLC患者铂类化疗后有效率分别为36.9%(38/103)和22.8%(23/101),两者比较差异有统计学意义(P<0.05)。XRCC1(399)G/G基因型患者对顺铂类药物的敏感性是G/A+A/A基因型患者的1.983倍(95%可信区间(CI):1.073~3.662,P=0.028)。携带XRCC1(399)G/G、G/A+A/A基因型的NSCLC患者铂类化疗后中位生存期(MST)、1年生存率及2年生存率分别为12.0月、52.4%、11.7%和10.0月、37.6%、3.0%,两者比较差异均有统计学意义(P<0.05)。结论 XRCC1(399)基因多态性与晚期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 XRCC1 and survival of patients with advanced non-small cell lung cancer( NSCLC) treated with platinum-based chemotherapy. Methods A total of 204 patients with advanced NSCLC were routinely treated by platinum-based chemotherapy. The genotypes were analyzed by MALDITOF-MS method using DNA samples isolated from peripheral blood before treatment. Besides,5% of the samples were extracted randomly for sequencing to test the accuracy of this method. The association between SNPs of XRCC1( 399) and prognosis to platinum-based chemotherapy in the patients with advanced NSCLC was analyzed. Results Of 204 patients,61 achieved partial response,116 achieving stable response,and 27 having progressive disease. The overall effective rate was 29. 9%( 61 /204), and the ineffective rate was 70. 1%( 143 /204). The effective rates of patients with XRCC1( 399) G/ G genotype and G/ A + A/ A genotype were 36. 9%( 38 /103) and 22. 8%( 23 /101),respectively( P < 0. 05). The sensitivity to DDP of XRCC1( 399) G/ G allele carriers was 1. 983-fold of that of G/ A + A/ A allele carriers( 95% confidence interval CI: 1. 073 ~ 3. 662,P = 0. 028). Median survival time,1-year survival and 2-year survival rates of patients with XRCC1( 399) G/ G genotype and G/ A + T / T genotype were 12. 0 months,52. 4% and 11. 7% and 10. 0 months,37. 6% and 3.0%,respectively( P < 0. 05). Conclusions Polymorphisms of XRCC1 might be associated with overall survival period in patients with advanced NSCLC after treatment with platinumbased chemotherapy,which might be the predictive markers for overall survival.

关 键 词：单核苷酸多态性 非小细胞肺癌 铂类药物联合化疗 生存期 

分 类 号：R734.2[医药卫生—肿瘤]