Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, FuCheng Road 52, HaiDian District, Beijing, China.
Cancer Chemother Pharmacol. 2013 Aug;72(2):305-14. doi: 10.1007/s00280-013-2194-x. Epub 2013 May 22.
The association between glutathione-S-transferase P1 (GSTP1) Ile105Val polymorphism and oxaliplatin-induced neuropathy has been investigated in a number of published studies. However, most of these studies were based on small sample sizes and the results remained inconsistent. To assess the relationship between GSTP1 gene Ile105Val polymorphism and its susceptibility to oxaliplatin-induced neuropathy, a meta-analysis of previous studies was conducted.
Two investigators independently searched studies published up to December 2012 from the databases of PubMed, EMBASE and The Cochrane Library. The pooled effect was calculated as odds ratio (OR) and corresponding 95 % confidence intervals (CIs) using fixed-effect or random-effect model.
Twelve prospective trials and two retrospective clinical trials involving 2,191 participants met the inclusion criteria. Combined analyses of these studies showed no significant associations between GSTP1 Ile105Val polymorphism and oxaliplatin-induced neuropathy, yielding OR of 1.08 (95 %CI 0.67-1.74, P = 0.754) in dominant model. Similar results were also obtained in recessive model (OR = 1.67, 95 %CI 0.56-4.93, P = 0.357) and allelic analysis (OR = 1.22, 95 %CI 0.67-2.24, P = 0.513). Since significant heterogeneity across studies, the pooled effects were calculated by random-effect model. No evidence of publication biases was identified in this meta-analysis.
This meta-analysis did not support the hypothesis that GSTP1 Ile105Val polymorphism was related to the occurrence of neurotoxicity in oxaliplatin-treated patients. Given the limited number of studies and potential bias, large-scale and well-designed clinical trials should be needed to confirm these hypotheses.
谷胱甘肽 S-转移酶 P1(GSTP1)Ile105Val 多态性与奥沙利铂诱导的周围神经病变之间的关联已在许多已发表的研究中进行了探讨。然而,大多数这些研究都是基于小样本量,结果也不一致。为了评估 GSTP1 基因 Ile105Val 多态性与奥沙利铂诱导的周围神经病变易感性之间的关系,对以前的研究进行了荟萃分析。
两位研究者独立检索了截至 2012 年 12 月从 PubMed、EMBASE 和 The Cochrane Library 数据库中发表的研究。使用固定效应或随机效应模型计算合并效应为比值比(OR)和相应的 95%置信区间(CI)。
符合纳入标准的有 12 项前瞻性试验和 2 项回顾性临床试验,共涉及 2191 名参与者。对这些研究的综合分析显示,GSTP1 Ile105Val 多态性与奥沙利铂诱导的周围神经病变之间无显著相关性,在显性模型中 OR 为 1.08(95%CI 0.67-1.74,P=0.754)。在隐性模型(OR=1.67,95%CI 0.56-4.93,P=0.357)和等位基因分析(OR=1.22,95%CI 0.67-2.24,P=0.513)中也得到了类似的结果。由于研究之间存在显著的异质性,因此采用随机效应模型计算合并效应。本荟萃分析未发现发表偏倚的证据。
本荟萃分析不支持 GSTP1 Ile105Val 多态性与奥沙利铂治疗患者发生神经毒性相关的假设。鉴于研究数量有限且存在潜在偏倚,需要进行大规模、精心设计的临床试验来验证这些假设。