XRCC1基因Arg399Gln位点多态性对卵巢癌患者铂类药物化疗敏感性及临床预后影响的Meta分析

Effects of XRCC1 Arg399Gln Gene Polymorphism on Platinum-based Chemotherapy Sensitivity and Clinical Prognosis in Patients with Ovarian Cancer:A Meta-analysis

目的:系统评价DNA修复基因X线修复交叉互补1(XRCC1)基因Arg399Gln位点多态性对卵巢癌患者铂类药物化疗敏感性及临床预后的影响,为临床提供循证参考。方法:计算机检索Embase、Medline、Cochrane图书馆、中文科技期刊数据库、中国期刊全文数据库、中国生物医学文献数据库和万方数据库,收集XRCC1基因Arg399Gln位点多态性与卵巢癌患者对以铂类药物为基础的联合化疗方案的敏感性及其临床预后的相关性的队列研究,提取资料并按照纽卡斯尔-渥太华量表评价质量后,采用Stata12.0统计软件进行Meta分析。结果:共纳入5项研究,合计681例卵巢癌患者。按照XRCC1基因Arg399Gln位点多态性检测结果分为野生型(Arg/Arg)、突变杂合型(Arg/Gln)和突变纯合型(Gln/Gln)。Meta分析结果显示,Arg/Gln型与Arg/Arg型[OR=1.01,95%CI(0.23,4.55),P=0.977]、Gln/Gln型与Arg/Arg型[OR=0.97,95%CI(0.12,7.63),P=0.969]、Arg/Gln+Gln/Gln型与Arg/Arg型[OR=0.95,95%CI(0.19,4.69),P=0.948]、Arg/Arg+Arg/Gln型与Gln/Gln型[OR=1.06,95%CI(0.34,3.32),P=0.920]、Arg/Arg+Gln/Gln型与Arg/Gln型[OR=0.92,95%CI(0.45,1.88),P=0.829]、携带Arg与Gln等位基因[OR=0.92,95%CI(0.33,2.56),P=0.877]卵巢癌患者的化疗敏感性比较,差异均无统计学意义。Arg/Gln型与Arg/Arg型[HR=1.09,95%CI(0.79,1.52),P=0.592]、Gln/Gln型与Arg/Arg型[HR=1.16,95%CI(0.35,3.82),P=0.812]卵巢癌患者的总生存期比较,差异均无统计学意义。仅有1项研究显示XRCC1基因Arg399Gln位点多态性与卵巢癌患者的无进展生存期无关(P>0.05)。结论:XRCC1基因Arg399Gln位点多态性与卵巢癌患者对以铂类药物为基础的联合化疗方案的敏感性及临床预后无关,该位点多态性不能作为卵巢癌患者化疗敏感性及临床预后的判断指标。

OBJECTIVE:To evaluate the effects of DNA repair gene XRCC1 Arg399Gln polymorphism on platinum-based chemotherapy sensitivity and clinical prognosis in patients with ovarian cancer,and to provide evidence-based reference for clinical treatment.METHODS:Retrieved from Embase,Medline,Cochrane Library,VIP,CNKI,CBM and Wanfang database,cohort studies on the relationship of XRCC1 gene Arg399Gln polymorphism with platinum-based combination chemotherapy sensitivity and clinical prognosis in patients with ovarian cancer were collected.Meta-analysis was performed by using Stata 12.0 statistical software after data extraction and quality evaluation with Newcastle-Ottawa scale.RESULTS:A total of 5 studies were included,involving 681 patients with ovarian cancer.According to the detection results of XRCC1 gene Arg399Gln polymorphism,they were divided into wild genotype(Arg/Arg),mutant heterozygote genotype(Arg/Gln)and mutant homozygote genotype(Gln/Gln).Results of Meta-analysis showed that there was no statistical significance in chemotherapy sensitivity between Arg/Gln genotype and Arg/Arg genotype[OR=1.01,95%CI(0.23,4.55),P=0.977],Gln/Gln genotype and Arg/Arg genotype[OR=0.97,95%CI(0.12,7.63),P=0.969],Arg/Gln+Gln/Gln genotype and Arg/Arg genotype[OR=0.95,95%CI(0.19,4.69),P=0.948],Arg/Arg+Arg/Gln genotype and Gln/Gln genotype[OR=1.06,95%CI(0.34,3.32),P=0.920],Arg/Arg+Gln/Gln genotype and Arg/Gln genotype[OR=0.92,95%CI(0.45,1.88),P=0.829],Arg and Gln allele[OR=0.92,95%CI(0.33,2.56),P=0.877]of patients with ovarian cancer.There was no statistical significance in overall survival time between Arg/Gln genotype and Arg/Arg genotype[HR=1.09,95%CI(0.79,1.52),P=0.592],Gln/Gln genotype and Arg/Arg genotype[HR=1.16,95%CI(0.35,3.82),P=0.812]of patients with ovarian cancer.Only one study showed that XRCC1 gene Arg399Gln polymorphism was not associated with progression-free survival time in patients with ovarian cancer(P>0.05).CONCLUSIONS:XRCC1 gene Arg399Gln polymorphism is not associated with platinum-based chemotherapy sensitivity and clinical prognosis in patients with ovarian cancer;its polymorphism can not be used as judgment index for chemotherapy sensitivity and clinical prognosis in patients with ovarian cancer.