目的:本荟萃分析的目的是评估基因多态性对铂类化疗(PBC)诱导的耳毒性的影响。
方法:PubMed的系统搜索,Embase,科克伦,和WebofScience是从数据库创建到2022年5月31日进行的。还审查了会议的摘要和介绍。
方法:4名研究者根据系统评价和荟萃分析指南的首选报告项目独立提取数据。分析了参考和变体(i)基因型和(ii)等位基因之间PBC诱导的耳毒性的患病率差异。使用随机效应模型将总体效应大小表示为比值比(OR),置信区间为95%(CI)。
结果:从包含的32篇文章中,在28个基因上鉴定出59个单核苷酸多态性,共有4406名独特参与者。对于等位基因频率分析,ACYP2rs1872328中的A等位基因与耳毒性呈正相关(OR:2.61;95%CI:1.06-6.43;n=2518)。在仅限于顺铂使用时,COMTrs4646316和COMTrs9332377的T等位基因显示出明显的结果。对于基因型频率分析,ERCC2rs1799793的CT/TT基因型表现出耳保护作用(OR:0.50;95%CI:0.27-0.94;n=176).排除使用卡铂或伴随放疗的研究显示,COMTrs4646316,GSTP1rs1965和XPCrs2228001具有显着的作用。研究之间差异的主要来源包括患者人口统计学的差异,耳毒性分级系统,和治疗方案。
结论:我们的荟萃分析显示多态性在接受PBC的患者中具有耳毒性或耳保护作用。重要的是,这些等位基因中的几个在全球范围内以高频率被观察到,强调个性化护理的多基因筛查和累积风险评估的潜力。
The objective of this meta-analysis is to evaluate the impact of genetic polymorphisms on platinum-based chemotherapy (PBC)-induced ototoxicity.
Systematic searches of PubMed, Embase, Cochrane, and Web of Science were conducted from the inception of the databases to May 31, 2022. Abstracts and presentations from conferences were also reviewed.
Four investigators independently extracted data in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Differences in the prevalence of PBC-induced ototoxicity between reference and variant (i) genotypes and (ii) alleles were analyzed. The overall effect size was presented using the random-effects model as an odds ratio (OR) with a 95% confidence interval (CI).
From 32 included articles, 59 single nucleotide polymorphisms on 28 genes were identified, with 4406 total unique participants. For allele frequency analysis, the A allele in ACYP2 rs1872328 was positively associated with ototoxicity (OR: 2.61; 95% CI: 1.06-6.43; n = 2518). Upon limiting to cisplatin use only, the T allele of COMT rs4646316 and COMT rs9332377 revealed significant results. For genotype frequency analysis, the CT/TT genotype in ERCC2 rs1799793 demonstrated an otoprotective effect (OR: 0.50; 95% CI: 0.27-0.94; n = 176). Excluding studies using carboplatin or concomitant radiotherapy revealed significant effects with COMT rs4646316, GSTP1 rs1965, and XPC rs2228001. Major sources of variations between studies include differences in patient demographics, ototoxicity grading systems, and treatment protocols.
Our meta-analysis presents polymorphisms that exert ototoxic or otoprotective effects in patients undergoing PBC. Importantly, several of these alleles are observed at high frequencies globally, highlighting the potential for polygenic screening and cumulative risk evaluation for personalized care.