切除修复交叉互补基因1多态性与铂类药物诱导周围神经病变相关性的系统评价

Meta-analysis on Correlation Between Excision Repair Cross-complementing Gene 1 and Peripheral Neuropathy Induced by Platinum

目的:系统评价切除修复交叉互补基因1(exeision repair cross-compietionl 1,ERCC1)多态性与铂类药物诱导周围神经病变的相关性。方法:计算机检索PubMed、Embase、Cochrane Library、中国生物医学文献数据库、中国学术期刊全文数据库及万方数据库自建库至2016年12月所有相关文献,收集有关ERCC1基因多态性与铂类药物诱导周围神经病变的相关性研究,采用Rev Man 5.3软件进行文献荟萃(Meta)分析。结果:共纳入11篇文献,其中涉及ERCC1的2个位点,分别为ERCC1 118C/T、ERCC1 8092C/A。Meta分析结果显示,ERCC1 118C/T位点各种遗传模型的比较均提示,发生任何程度的周围神经病变与ERCC1118C/T位点基因多态性均无明显关联,药物、人种的亚组分析也没有显示出明显的关联性。ERCC1 8092C/A位点出现1个阳性结果,在结局指标为发生≥3级周围神经病变时,显性模型分析结果的合并OR=2.70(95%CI=1.37~5.31),表明携带基因型(AA+CA)人群发生铂类药物诱导的≥3级PN的发病危险性高于基因型CC人群。结论:ERCC1 8092C/A位点有至少1个A突变的基因型的人群可能更容易发生铂类药物诱导的≥3级周围神经病变。但本研究纳入文献数量有限,样本数量较小,缺乏代表性,且多为观察性研究,尚需大样本、多中心、精心设计的临床试验以证实并完善本研究的结论。

OBJECTIVE：To systematically review the correlation between excision repair cross-complementing gene 1 （ ERCC1 ） and peripheral neuropathy （ PN） induced by platinum .METHODS：Relevant literatures published up to Dec.2016 were retrieved from PubMed, Embase, Cochrane Library, China Biology Medicine disc, CNKI and Wanfang database , studies on correlation between ERCC 1 and PN induced by platinum were collected , and Meta-analysis was conducted by using RevMan 5.3 software .RESULTS：A total of 11 studies were included , involving two locus of ERCC1, respectively were ERCC1118C/T and ERCC18092C/A.According to Meta-analysis, various genetic models of ERCC1118C/T locus all showed that there was no significant correlation between PN and ERCC 1118C/T gene polymorphism, subgroup analysis of drugs and ethnic also did not show significant relevance .ERCC18092C/A showed a positive result , the combination of dominant model analysis was OR=2.70 （95%CI=1.37-5.31） when the outcome peripheral neuropathy was ≥3 grade , which indicated that the incidence of PN of ≥3 grade induced by platinum among people with genotype of （ AA ＋CA ） was higher than of people with genotype of CC . CONCLUSIONS：People whom have at least 1 A-gene mutation type at the ERCC 18092 C/A locus are more likely to be involved in PN of ≥3 grade induced by platinum drugs .However , the number of included literatures is limited , small sample size with lacks of representativeness , of which are mostly observational studies .Further clinical tests with large sample size , multiple centers and meticulous designs are needed to verify and perfect this conclusion .