DNA修复基因多态性与肺癌顺铂化疗敏感性的研究  

Association of DNA repair gene polymorphisms with response to platinum-based chemotherapy in patients with non-small cell lung cancer

作　　者：李代蓉[1] 杨燕青[2] 田玲[1] 王莉[1] 马惠文[1] 李启英[1] 黄新华[2] 

机构地区：[1]重庆市肿瘤研究所肿瘤内科,重庆400030 [2]生物芯片上海国家工程研究中心,上海201203

出　　处：《肿瘤》2011年第4期348-353,共6页Tumor

基　　金：重庆市卫生局基金资助项目(编号:07-2-180)

摘　　要：目的:研究切除修复交叉互补基因1(excision repair cross-complementing gene 1,ERCC1)Asn118Asn、切除修复交叉互补基因2(excision repair cross-complementing gene 2,ERCC2)Lys751Gln和X线修复交叉互补基因1(X-ray repair cross complementing group 1,XRCC1)Arg399Gln单核苷酸多态性与非小细胞肺癌(non-small cell lung cancer,NSCLC)对铂类药物化疗敏感性的相关性。方法:采用基因测序的方法,检测89例以铂类药物为主要化疗方案的NSCLC患者外周血DNA中ERCC1基因Asn118Asn、ERCC2基因Lys751Gln和XRCC1基因Arg399Gln的基因型;采用统计学方法分析不同基因型与化疗疗效的相关性。结果:89例NSCLC患者采用铂类药物化疗总有效率为29.2%;ERCC1基因Asn118Asn和ERCC2基因Lys751Gln基因型在化疗有效组和无效组之间的分布,差异无统计学意义(P>0.05);而携带XRCC1基因Arg399Arg与携带至少1个Gln等位基因(Arg399Gln和Gln399Gln)基因型患者的有效率分别为76.9%和23.1%(χ2=11.1,P=0.001)。携带XRCC1基因Arg399Arg基因型患者对化疗的敏感性明显高于携带至少1个Gln等位基因型的患者(比值比为5.228,95%可信区间为1.776～15.387,P=0.003)。ERCC1、ERCC2和XRCC1基因型的联合可以提高化疗的有效率。结论:ERCC1、ERCC2和XRCC1基因的单核苷酸多态性的联合可能与NSCLC对铂类药物化疗敏感性具有相关性。Objective：To investigate the correlations of single nucleotide polymorphisms（SNPs） of excision repair cross-complementing gene 1（ERCC1） Asn118Asn,excision repair cross-complementing gene 2（ERCC2） Lys751Gln and the X-ray repair cross-complementing group 1（XRCC1） Arg399Gln with the response to platinum-based chemotherapy in patients with non-small cell lung cancer（NSCLC）.Methods：The gene sequence analysis was used to determine the SNPs of ERCC1 Asn118Asn,ERCC2 Lys751Gln and XRCC1 Arg399Gln in the human peripheral lymphocyte DNAs from 89 patients with NSCLC treated with 2 cycles of platinum-based chemotherapy.The correlations of ERCC1 Asn118Asn,ERCC2 Lys751Gln and XRCC1 Arg399Gln SNPs with the chemosensitivity were analyzed.Results：The overall response rate of platinum-based chemotherapy in 89 NSCLC patients was 29.2%.The genotype distributions of ERCC1 Asn118Asn and ERCC2 Lys751Gln between the response group and the non-response group had no significant difference（P0.05）.The XRCC1 399Arg/Arg genotype carriers had higher response rate than the Gln genotype（Arg399Gln and Gln399Gln） carriers（76.9% and 23.1%,respectively,P=0.001;odds ratio =5.228,95% confidence interval =1.776-15.387,P=0.003）.Favorable genotypes from polymorphisms in ERCC1,ERCC2 and XRCC1 were involved in the better response to platinum-based chemotherapy in patients with NSCLC.Conclusion：The combination SNPs of ERCC1,ERCC2 and XRCC1 genes may be associated with the high sensitivity to platinum-based chemotherapy in patients with NSCLC.

关 键 词：癌 非小细胞肺 抗肿瘤联合化疗方案 多态性 单核苷酸 切除修复交叉互补基因1 切除修复交叉互补基因2 X线修复交叉互补基因1 

分 类 号：R730.43[医药卫生—肿瘤]