XRCC1基因Arg194Trp位点多态性与胃癌铂类药物化疗敏感性的关系

摘要

Objective To explore the correlation between X-ray cross complementing repair gene 1 (XRCC1) gene Arg194Trp polymorphism and platinum-based chemotherapy in patients with gastric cancer.Methods Eighty patients with gastric cancer who underwent platinum-based chemotherapy were selected,and the XRCC1 genotypes were detected by multiplex PCR and ligase detection reaction (LDR).All patients were treated with oxaliplatin-based first-line chemotherapy.Accorded to the curative effect standard of gastric cancer treatment,the patients were divided into the platinum sensitive group and platinum resistance group,and the correlation between XRCC1 gene Arg194Trp polymorphism and platinumbased chemotherapy was analyzed.Results There were three kinds of genotypes in XRCC1 gene Arg194Trp:Arg/Arg,Arg/Trp,and Trp/Trp,their distribution frequencies were 42.5％ (34/80),50％ (40/80),and 7.5％ (6/80),respectively.The proportional distribution of the three genotypes met genetic equilibrium law of Hardy-Weiberg,and the experimental subjects were representative.There were no significant differences in sex,age,histological type,TNM stage,chemotherapy regimen in patients with Arg/Arg,Arg/Trp,and Trp/Trp genetypes (all P ＞ 0.05).In 80 patients,platinum drug sensitivity (CR + PR) was found in 39 patients (48.8％),and platinum drug resistance (SD + PD) in 41 patients (51.2％).The sensitivity of platinum drugs in patients with Arg/Trp and Trp/Trp genotypes was significantly higher than that in patients with Arg/Arg genotype (P ＜ 0.05),and there was no significant difference between Arg/Trp and Trp/Trp genotypes in patients (P ＞0.05).Conclusion The XRCC1 gene Arg194Trp is related with the sensitivity of platinum-based drugs in patients with gastric cancer,and the detection of Arg194Trp polymorphism can provide a basis for individual chemotherapy of gastric cancer.%目的 探讨X射线损伤交叉互补蛋白1(XRCC1)Arg194Trp位点多态性与胃癌铂类药物化疗敏感性的关系.方法 选择接受铂类药物化疗的胃癌患者80例,采用聚合酶链式反应-连接酶检测反应技术检测XRCC1基因Arg194Trp位点基因型.所有患者术后接受以奥沙利铂为主的一线化疗方案,根据化疗效果分为化疗敏感者和化疗耐药者,分析XRCC1基因Arg194Trp位点多态性与化疗敏感性的关系.结果 XRCC1基因Arg194Trp位点存在Arg/Arg、Arg/Trp、Trp/Trp三种基因型,分布频率分别为42.5％(34/80)、50.0％(40/80)、7.5％(6/80);三种基因型分布满足Hardy-Weiberg基因遗传平衡定律,具有群体代表性.Arg/Arg、Arg/Trp、Trp/Trp基因型患者性别、年龄、组织类型、TNM分期、化疗方案等临床病理参数比较差异均无统计学意义(P均＞0.05).80例患者中,化疗敏感(完全缓解+部分缓解)39例(48.8％),耐药(稳定+进展)41例(51.2％);Arg/Trp、Trp/Trp基因型者化疗敏感率均显著高于Arg/Arg者(P均＜0.05),Arg/Trp与Trp/Trp基因型患者化疗敏感率比较差异无统计学意义(P＞0.05).结论 XRCC1基因Arg194Trp位点多态性与胃癌患者铂类药物化疗敏感性有关;检测Arg194Trp位点多态性可为胃癌化疗的个体化用药提供依据.