Association between GSTP1 Ile105Val polymorphism and oxaliplatin-induced neuropathy: a systematic review and meta-analysis

Cancer Chemother Pharmacol. 2013 Aug;72(2):305-14. doi: 10.1007/s00280-013-2194-x. Epub 2013 May 22.

Abstract

Background and aims: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Alleles
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Confidence Intervals
  • Genotype
  • Glutathione S-Transferase pi / genetics*
  • Humans
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / enzymology*
  • Neoplasms / complications
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Organoplatinum Compounds / adverse effects*
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Polymorphism, Genetic / genetics*
  • Prospective Studies
  • Publication Bias
  • Retrospective Studies

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin
  • GSTP1 protein, human
  • Glutathione S-Transferase pi