XRCC1基因多态性影响奥沙利铂对晚期胃癌患者化疗疗效敏感性的关系

Polymorphism of XRCC1 Gene Influences Response to Oxaliplatin-Based Chemotherapy in Patients with Advanced Gastric Cancer

目的:研究DNA修复酶X射线损伤交叉互补蛋白1(X-ray repair cross-complementary protein 1,XRCC1)基因Arg399Gln多态性与晚期胃癌对奥沙利铂化疗敏感性的关系。方法:确诊的晚期胃癌患者68例,接受以奥沙利铂为主的化疗方案化疗。采用PCR-连接酶反应技术检测XRCC1 Arg399Gln多态性。比较不同基因型患者与化疗疗效及疾病进展时间(TTP)的关系。结果:68例胃癌患者中,38例(55.9%)携带XRCC 1399Arg/Arg基因型,24例(35.3%)携带Arg/Gln基因型,6例(8.8%)携带Gln/Gln基因型。68例病人化疗总有效率(CR+PR)为48.5%(33/68),其中Arg/Arg基因型患者化疗有效率显著高于Arg/Gln+Gln/Gln基因型患者(60.5%vs 33.3%,χ2=4.963,P=0.026)。68例患者中位TTP为8.0个月,其中Arg/Arg基因型患者为10个月,Arg/Gln+Gln/Gln基因型患者7.5个月,两者比较差异有显著性(χ2=17.383,P<0.001)。结论:XRCC1 Arg399Gln基因可以在一定程度上判断晚期胃癌患者接受奥沙利铂化疗后的预后情况。

Objective To evaluate the relationship between genetic polymorphisms of XRCC1 Arg399Gln（G→A） and the response to oxaliplatin-based chemotherapy in patients with advanced gastric cancer.Methods A total of 68 patients with advanced gastric cancer（stage Ⅳ）were treated with oxaliplatin-based chemotherapy.XRCC1 Arg399Gln was determined with PCR-LDR（ligation detection reaction） technique.The influence of XRCC1 genotypes on the response rate and the time to progress（TTP） was explored.Results The frequencies of XRCC1 codon 399 Arg/Arg,Arg/Gln and Gln/Gln genotype were 55.9%,35.3% and 8.8%,respectively.The clinical response rate（CR＋PR） as a whole was 48.5%.Patients with Arg/Arg genotype showed significantly increased response rate than that in patients with Arg/Gln＋Gln/Gln（60.5% vs 33.3%,χ2=4.963,P=0.026）.The median TTP of all patients was 8 months,with 10 months for Arg/Arg genotype carriers and 7.5 months for Arg/Gln＋Gln/Gln carriers（χ2=17.383,P〈0.001）.Conclusion Determination of XRCC1 Arg399Gln gentypes may be useful as a prognostic indicator in patients with advanced gastric cancer treated with oxaliplatin-based chemotherapy.