【摘要】 目的探讨XRCC1基因Arg399Gln位点多态性与结直肠癌患者的铂类药物化疗敏感性和预后之间的关系。方法计算机检索PubMed、Embase、the Cochrane Library、Web of Science databases、CNKI、CBMdisc、Wanfang数据库,收集有关结直肠患者XRCC1 Arg399Gln位点多态性对以铂类药物为基础的联合化疗的有效性和临床结局的研究,采用Stata 15.1统计软件进行Meta分析。结果共纳入19项研究,合计2 382例患者。按照基因检测结果发现,XRCC1 Arg399Gln位点野生型(GG基因型),突变杂合型(AG基因型)和突变纯合型(AA基因型)。Meta分析结果显示,XRCC1 Arg399Gln位点多态性在显性、共显性遗传模型下与结直肠癌患者接受铂类化疗的敏感性有关(AA+AG vs GG:OR=0.50,95%CI:0.38～0.65,P=0.000;AG vs GG:OR=0.72,95%CI:0.53～0.98,P=0.038;AA vs GG:OR=0.34,95%CI:0.18～0.67,P=0.002)。在剔除Gan等的研究后按照种族亚组分析提示,XRCC1 Arg399Gln位点多态性在显性遗传模式下与亚洲人群结直肠癌患者铂类药物化疗的敏感性有关(AA+AG vs GG:OR=0.43,95%CI:0.32～0.58, P=0.000),而在高加索人群中无明显相关性。在所有纳入的研究中显示XRCC1 Arg399Gln位点在显性和共显性遗传模式下与结直肠癌患者的无进展生存期(PFS)和总生存率(OS)无明显相关性。结论 XRCC1基因Arg399Gln位点多态性与亚洲人群结直肠癌患者以铂类药物为基础的化疗敏感性有关,而与化疗后的PFS和OS无明显相关性。更多还原

【Abstract】 Objective To evaluate the effects of DNA repair gene XRCC1 Arg399Gln polymorphism on platinum-based chemotherapy sensitivity and clinical prognosis in patients with colorectal cancer(CRC). Methods Studies on the relationship of XRCC1 Arg399Gln polymorphism with platinum-based combination chemotherapy sensitivity and clinical prognosis in patients with CRC were retrieved from PubMed, Embase, the Cochrane Library, Web of Science databases, CNKI, CBMdisc and Wan Fang.Meta-analysis was performed by using Stata 15.1 statistical software after data extraction and quality evaluation with NOS.Results A total of 19 studies were included, involving 2382 patients with CRC. According to the detection results of XRCC1 Arg399Gln polymorphism, they were divided into wild genotype(GG), mutant heterozygote genotype(AG) and mutant homozygote genotype(AA). Heterogeneity analysis revealed that there was significant difference in chemotherapy sensitivity between dominant and codominance genetic patterns(AA+AG vs GG, OR=0.50, 95%CI: 0.38, 0.65, P=0.000; AG vs GG, OR=0.72, 95%CI: 0.53,0.98, P=0.038; AA vs GG, OR=0.34, 95%CI: 0.18,0.67, P=0.002). After removal of Gan’s study the results of subgroup analysis showed that XRCC1 Arg399Gln polymorphisms correlated with chemotherapy sensitivity in patients with dominant genetic pattern(AA+AG vs GG, OR=0.43, 95%CI: 0.32, 0.58, P=0.000) in Asian patients. There was no significant association between XRCC1 Arg399Gln polymorphism and hazard for PFS and OS for CRC patients in all tested models. Conclusion XRCC1 Arg399Gln polymorphism is associated with platinum-based chemotherapy sensitivity in Asian patients with CRC, while there was no significant difference in the OS and PFS.更多还原