DNA修复基因ERCC1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

Polymorphisms of excision repair cross - complementation group 1 and its association with survival to platinum- based chemotherapy in advanced non- small cell luIlg cancer

目的探讨DNA修复基因ERCC1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，化疗前采集患者外周血。采用基因芯片法检测ERCC1（118）、（504）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，与基冈测序结果完全吻合。中位随访时间11个月。携带ERCCl（118）C／C、C／T＋rr／T基凶型患者铂类药物化疗后中位牛存期（MSq、），1年、2年及3年牛存率分别为10．9个月、35．9％、6．3％、1．6％和13．5个月、59．5％、19．0％、14．3％，2组间差异均有统计学意义（P〈0．05或P〈0．01）；携带ERCC1（504）C／C基因型、C／A＋，A／A基因型1年生仔率、2年牛存率分别为66．7％、16．8％和31．3％、7．8％，2组间差异均有统计学意义（P〈0．05或P〈0．01），而MST和3年生存率2组间差异尤统计学意义（P〉0．05）。结论 该芯片检测方法准确，高通量，价卡2}低廉，适用于大规模样本SNP检测，ERCC1（118）基因多态性与NSCLC患者铂类约物化疗后的生存期有关，有可能作为铂类约物化疗后生存期的预测指标。

Objective To investigate the relationship between genetic polymorphisrns of excision repair cross - eom- plementation group 1 （ERCC1） 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 NSCI,C were routinely treated by cisplatin - or carboplatin - hosed chemotherapy, The polymorphie genotypes were analyzed by gene - chip method using DNA samples isolated from peripheral blood before treatment. Besides, 10% samples were extracted randomly for se- quencing to test the accuracy of this method. To explored the association between single nueleotide polymorphism （SNP） of ERCCI （118） ,ERCCI （504） and progrmsis In plat inmn- based chemotherapy in advanced NSCLC patients. Results Homozygous wild type, heterozygote type and hemozyguus mutant type yielded green, yellow and red fluorescence, re- spectively, the resuhs were according to gene sequencing. Median follow - up period was l l months. Mean survival time （ MST）, 1 - year survival ,2 - year survival and 3 - year survival rates of patients with the ERCCI （ 118 ） C/C genotype, C/T ＋ T/T genotype were 10.9 months, 35.9% , 6.3% , and 1.6% vs. 13.5 months, 59.5% , 19.0% , and 14.3% , respectively, with significant difference（ P 〈 0.05 or P 〈 0.01 ）. 1 - year survival , 2 - year survival rate of patients with the ERCC1 （504） C/C genotype and C/A ＋ A/A genotype were 66.7%, 16.8% vs. 31.3%, 7.8% ,respectively, with signiticant difference（ P 〈 0.05 ）. MST and 3 - year survival rates were no significant difference（P 〉 0.05 ）. Conclusion The DNA mieroan＇ay - based method is accurate, high - throughput and inexpensive, suitable for SNP genotyping in a large number of samples. Polymorphisms of ERCC1 （118） mlight be associated with overall survival period in patients with advanced NSCLC after treatmem with platin - based chemotherapy, which might be the predictive markers for overall survival.