DNA修复基因ERCC1单核苷酸多态性预测非小细胞肺癌铂类药物化疗敏感性

目的 探讨DNA修复基因ERCC1(Excision repair cross-complementation group 1)单核苷酸多态性预测晚期非小细胞肺癌(NSCLC)铂类药物[顺铂(DDP)或卡铂(CBP)]化疗敏感性的可行性.方法 经病理学确诊的NSCLC患者117例,采用DDP或CBP为基础药物的方案化疗,3个周期后进行疗效评价.以聚合酶链反应结合限制性片段长度多态性(PCR-RFLP)检测DNA修复基因ERCC1基因型,并分析基因型与化疗敏感性的关系.结果 (1)ERCC1(Asn118Asn)携带至少一个C等位基因基因型的患者(C/C,C/T)铂类化疗有效率更高(Odds ratio=0.19;95%CI:0.041～0.872;P＜0.05);(2)ERCC1(C8092A)多态性与生存期相关(P＜0.05),携带至少一个A等位基因基因型的患者(C/A,A/A)的中位生存期长于其他基因型(16比9月);(3)ERCC1基因多态性(C8092A和N118N)可独立联合预测铂类化疗患者的生存期(OR=4.37;95%CI:1.26～15.23;P＜0.05).结论 ERCC1单核苷酸多态性可以预测NSCLC铂类药物的化疗敏感性.

Single nucleotide polymorphisms in DNA repair gene ERCC1 predict clinical response to platinumbased chemotherapy in non-small cell lung cancer

Objective To assessed whether single nucleotide polymorphisms (SNP) of DNA-repair genes ERCC1 predict efficacy and prognosis of non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Methods A retrospective dataset of 117 patients with NSCLC were routinely treated with cisplatin (DDP) or carboplatin (CBP) based regimens as first-or second-line chemotherapy. The allelotyping of DNA-repair genes polymorphisms were determined via PCR-RFLP using genomic DNA obtained from peripheral WBC. Results ERCC1 (Asn118Asn) genotype was significantly associated with response to treatment. Patients with either one or two C alleles (C/C, C/T) at Asn118Asn were more likely to respond to platinum-based chemotherapy compared with those without the C allele (Odds ratio = 0.19; 95% CI: 0.041-0.872; P＜ 0.05, by binary logistic regression). There was a significant association between the ERCC1 C8092A polymorphism and OS (P＜0.05, by log-rank test), with median survival times of 9 (C/C) and 16 (C/A or A/A) months, respectively,suggesting that any copies of the A allele were associated with an improved outcome. Cox's multivariate analysis suggested that the joint effect of ERCC1 polymorphic variants (C8092A and N118N) (Odds ratio, 4. 37; 95% CI: 1.26-15. 23;P＜0.05) was independent prognostic factors for OS in advanced NSCLC patients treated with platinumbased chemotherapy. Conclusion Assessment of genetic variations of ERCC1 could predict platinum-based chemotherapy outcome in advanced NSCLC.