切除修复交叉互补基因1 C8092A位点多态性对肺癌铂类药物化疗疗效的影响

Impact of ERCC1 C8092A gene polymorphism on the efficacy of platinum-based chemotherapy for lung cancer

目的探讨切除修复交叉互补基因1(excision repair cross complementing1,ERCC1)C8092A位点多态性与肺癌铂类药物化疗疗效及预后的关联,为肺癌精准治疗提供理论基础。方法选取从2014年1月至2017年10月,海口市2家三甲医院经病理学确诊为肺癌,且以铂类为基础化疗的肺癌患者120例作为研究对象,获得知情同意后采血,提取外周血DNA,质谱法检测ERCC1 C8092A位点基因型;采用WHO实体瘤临床疗效评价标准对患者的化疗疗效进行判定,通过电话随访等方式获得患者的生存情况。结果120例肺癌患者中,ERCC1 C8092A位点基因型频率分布为野生型CC 67例(55.8%)、杂合型CA 45例(37.5%)和突变型AA 8例(6.7%),符合Hardy-Weinberg遗传平衡定律(χ^(2)=0.140,P>0.05);总的化疗有效率为32.5%,ERCC1 C8092A位点CA基因型患者的化疗有效率最高(42.2%),CC基因型最低(25.4%)。研究对象总的1年生存率为68.3%,3年生存率为35.8%,携带ERCC1 C8092A AA基因型的患者生存率最低,其中1年生存率50.0%,3年生存率仅为25.0%;然而,3种ERCC1 C8092A基因型携带者间的总生存率差异无统计学意义(χ^(2)=0.328,P=0.849)。结论ERCC1 C8092A位点多态性与肺癌铂类化疗疗效相关联,CA基因型化疗有效率最高,CC基因型的肺癌患者1年、3年生存率明显高于CA和AA基因型。

Objective To explore the relationship between the polymorphism of excision repair cross-complementation group 1(ERCC1)C8092A locus and the efficacy and prognosis of platinum-based chemotherapy for lung cancer(LC),and to provide a theoretical basis for precision treatment of LC.Methods From January 2014 to October 2017,120 patients from two tertiary hospitals in Haikou City,and with pathologically confirmed lung cancer treated with platinum-based chemotherapy were selected as the research objects.After informed consent was obtained,peripheral blood samples were collected for DNA extraction,and the genotype of ERCC1 C8092A locus was detected by mass spectrometry.WHO's Response Evaluation Criteria in Solid Tumours(RECIST)was used to judge patients'chemotherapy efficacy and patients'survival status was obtained by telephone follow-up and other means.Results Among the 120 LC patients,the genotype frequencies of ERCC1 C8092A lo⁃cus were 67 cases of CC wildtype(55.8%),45 cases of CA heterozygous type(37.5%),and 8 cases of AA rare mutation type(6.7%),which conformed to Hardy-Weinberg equilibrium(χ^(2)=0.140,P>0.05).The total effective rate of chemotherapy was 32.5%,with the highest effective rate in patients with the CA genotype(42.2%)at the ERCC1 C8092A locus and the lowest in patients with the CC genotype(25.4%).The overall one-year survival rate was 68.3%and the three-year survival rate was 35.8%.The patients with ERCC1 C8092A AA genotype had the lowest survival rate,with a one-year survival rate of 50.0%and three-year survival rate of only 25.0%.However,there were no statistical differences in the overall survival rate among the three genotypes of carriers of ERCC1 C8092A(χ^(2)=0.328,P=0.849).Conclusions The polymorphism of ERCC1 C8092A lo⁃cus is associated with the efficacy of platinum-based chemotherapy for LC,and patients with CA genotype have the highest effi⁃cacy.The one-year and three-year survival rates of patients with CC genotype are significantly higher than those of CA and AA genotypes.