DNA修复基因多态性影响晚期胃癌卡培他滨联合奥沙利铂化疗的临床预后

摘要

目的:探讨DNA修复基因(ERCC1、ERCC2、XRCC1)单核苷酸多态性对胃癌患者卡培他滨联合奥沙利铂化疗敏感性的相关性.方法:本回顾性研究选取XELOX作为一线化疗方案的100例晚期胃癌患者为研究对象,检测分析三个基因六个单核苷酸多态性位点(ERCC1 rs11615;ERCC2 rs13181,rs1799793;XRCC1 rs25487,rs25489,rs1799782),同时分析其与临床预后的关系.结果:XRCC1 rs25487的A/G等位基因频率、AG/AA/GG基因分布频率均与疾病化疗敏感性和无进展生存期有关,携带GG基因型患者疗效好(P<0.05),中位PFS为8.00个月(95%CI:6.34~9.66);ERCC2 rs13181的G/T等位基因频率、GG/GT/TT基因分布频率与疾病化疗敏感性和无进展生存期明显相关,携带TT基因型患者疗效好(P<0.05),中位PFS为7.46个月(95%CI:6.45~8.48).COX比例风险模型显示ERCC2 rs13181 G/T基因型是晚期胃癌无进展生存期的独立风险因素之一(HR=0.72,95%CI:0.53~0.97,P=0.025).结论:ERCC2 rs13181基因多态性可能是评估接受XELOX化疗晚期胃癌患者预后的关键指标.%Objective:To investigated the associations between genetic polymorphisms of three genes involved in DNA repair and clinical outcomes in MGC patients receiving XELOX treatment.Methods:This retrospective study in-cluded 100 Chinese MGC patients receiving XELOX as first-line chemotherapy.Six single nucleotide polymorphisms (SNPs)of three genes (ERCC1 rs11615,ERCC2 rs13181 and rs1799793,and XRCC1 rs25487,rs25489,and rs1799782)were genotyped,and the associations between each SNP and clinical outcome were analyzed.Results:XRCC1 rs25487 A allele was significantly associated with progression disease (PD)to chemotherapy,and patients with GG genotype had significantly better progression-free survival (PFS)(8 months,95% CI:6.34 ~ 9.66,P <0.05)compared with patients with the G allele (AA + GA).ERCC2 rs13181 G allele was significantly associated with PD,and TT homozygotes tended to have better PFS(7.46 months,95% CI:6.45 ~ 8.48,P< 0.05)than carriers (GG + GT).ERCC2 rs13181 G/ T gene type were finally included in the COX regression model with a significance level of P< 0.05(HR = 0.72,95% CI:0.53 ~ 0.97,P = 0.025).Conclusion:These results suggest that the prognos-tic index comprising XRCC1 rs13181 polymorphisms may be a useful predictor of clinical outcomes in MGC treated with XELOX.