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DNA修复基因多态性与肺癌顺铂化疗敏感性的研究 被引量:11

Association of DNA repair gene polymorphisms with response to platinum-based chemotherapy in patients with non-small cell lung cancer
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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.
出处 《肿瘤》 CAS CSCD 北大核心 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)
关键词 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 Carcinoma non-small cell lung Antineoplastic combined chemotherapy protocols Polymorphism single nucleotide Gene ERCC1 Gene ERCC2 Gene XRCC1
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参考文献22

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