ERCC1和XRCC1多态性与进展期非小细胞肺癌对铂类化疗的敏感性

目的探讨DNA修复基因ERCC1 118C/T和XRCC1 Arg194Trp多态性与进展期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者铂类药物化疗敏感性的关系。方法采用PCR-RFLP技术检测149例经病理确诊的接受含铂两药方案化疗的NSCLC患者外周血ERCC1 118和XRCC1 194位点的基因型,并分析其与化疗疗效的关系。结果经2个周期化疗后,149例进展期NSCLC患者化疗有效率为32.9%。携带至少1个ERCC1 118T突变基因患者的化疗有效率至少是C/C野生型基因携带者的3倍(49.1%vs 23.4%,OR=3.156,95%CI:1.548～6.334,P=0.001)。携带至少1个XRCC1 194Trp突变基因患者的化疗有效率显著高于Arg/Arg基因型携带者(41.3%vs 23.2%,OR=2.326,95%CI:1.138～4.753,P=0.019)。ERCC1 118C/T和XRCC1 Arg194Trp 2个基因多态之间存在一定的联合作用,携带至少1个ERCC1 118 T突变基因同时又携带至少1个XRCC1 194Trp突变基因型者的化疗有效率明显高于同时携带ERCC1 118C/C和XRCC1 194Arg/Arg野生型基因者(66.7%vs 17.1%,OR=9.714,95%CI:3.104～30.406,P<0.001)。结论与单基因检测比较,2个基因的联合检测在预测铂类药物化疗敏感性中的价值更大。ERCC1 118和XRCC1 194基因多态联合与NSCLC患者对铂类药物化疗敏感性相关,ERCC1和XRCC1基因型的联合检测有可能成为预测铂类药物化疗敏感性的指标。

Sensitivity relationship of ERCC1 and XRCC1 genetic polymorphism on response of platinum-based chemotherapy in advanced NSCLC

Objective To investigate the relationship of genetic polymorphisms in excision repair cross-complementation group 1（ERCC1） 118 and X-ray repair cross-complementing group 1（XRCC1） 194 and the response to platinum-based chemotherapy in non-small cell lung cancer（NSCLC）.Methods A total of 149 advanced NSCLC patients who received platinum-based chemotherapy were analyzed in this study.Their DNA of peripheral blood leukocytes was extracted and ERCC1 118C/T,XRCC1 Arg194Trp genotypes were detected by the PCR-RFLP method in 149 patients with advanced NSCLC who received platinum-based chemotherapy.The relationship of ERCC1 and XRCC1 polymorphism with chemotherapy sensitivity was analyzed.Results After two chemotherapy cycles,the overall response rate in all patients was 32.9%.The patients with the ERCC1 118 C/T＋T/T polymorphisms were at least 3-folds more sensitive to the chemotherapy as those with the C/C genotype（49.1% vs 23.4%,OR=3.156,95%CI,1.548～6.334,P=0.001）.The response rate to the chemotherapy among the patients with XRCC1 194Trp allele was significantly higher than that among the patients with Arg/Arg genotype（41.3% vs 23.2%,OR=2.326,95%CI,1.138～4.753,P=0.019）.A cooperateive action effect between ERCC1 118 and XRCC1 194 polymorphisms was also found.The response rate to the therapy among the patients with 118 T allele and 194 Trp allele was significantly higher than that among the patients with ERCC1 118 C/C and XRCC1 194Arg/Arg genotype（66.7% vs 17.1%,OR=9.714,95%CI,3.104～30.406,P0.001）.Conclusions In comparison with the single genepolymorphism,the combined effect of ERCC1 and XRCC1 polymorphisms is more valuable in predicting the responses of the platinum-based chemotherapy.The polymorphisms of the ERCC1 and XRCC1 are associated with the clinical response to platinum-based chemotherapy in NSCLC,suggesting that the ERCC1 and XRCC1 genotypes could be used to predict the advanced NSCLC patients with better responses to platinum-based chemotherapy.