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

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

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.

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.