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-东南大学学报医学版

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

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出版年·卷·期（页码）：2011·30·第五期（717-721）

摘要：

目的探讨 DNA修复基因ERCC1、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11个月。携带ERCC1（118） C/C、C/T+T/T基因型患者铂类化疗后MST、1年、2年及3年生存率分别为10.9月、35.9%、6.3%、1.6%和13.5月、59.5%、19.0%、14.3%，两组间均有统计学差异（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月、59.1%、15.9%、6.8%和11.1月、35.5%、8.1%、6.5%，两组间均有统计学差异（P＜0.05）。结论该芯片检测方法准确，高通量,价格低廉，适用于大规模样本SNP检测，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，有可能作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 10.9months,35.9%,6.3% and 1.6% vs 13.5months,59.5%,19.0% and 14.3% respectively， with significant difference（p＜0.05）. 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（p＜0.05）.Conclusion The DNA microarray-based method is accurate, high-throughput and inexpensive, suitable for SNP genotyping in a large number of individuals .Polymorphisms of ERCC1、XRCC1 mlight 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.

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