Pharmacogenetic and ethnicity influence on oxaliplatin therapy for colorectal cancer: a meta-analysis

Pharmacogenomics. 2016 Oct;17(15):1725-1732. doi: 10.2217/pgs-2016-0102. Epub 2016 Sep 16.

Abstract

Aims: Oxaliplatin-based chemotherapy for colorectal cancer demonstrates interindividual variability in response, and polymorphisms of ERCC1, ERCC2, XRCC1, GSTP1 and GSTM1 genes may be contributing factors. Additionally, the effect of these genotypes may differ between ethnic groups. Material & Methods: A meta-analysis of the association between these genotypes and response, progression-free survival and overall survival (OS) for patients with colorectal cancer treated with oxaliplatin-based therapy is reported. Results: ERCC1 C118T (TT vs CC OS [hazard ratio (HR): 2.59; p = 0.001]), ERCC2 A2251C (CC or AC vs AA OS [HR: 1.53; p = 0.04]) and GSTP1 A313G (GG vs AA OS, [HR: 0.47; p < 0.001]) polymorphisms were associated with survival. The effect size may be larger for ERCC1 C118T and XRCC1 G1196A in Asian compared with Caucasian populations. No association was apparent for the GSTM1 genotype.

Conclusion: ERCC1 C118T, ERCC2 A2251C and GSTP1 A313G polymorphisms were associated with clinical outcomes.

Keywords: ERCC1; ERCC2; GSTM1; GSTP1; XRCC1; colorectal neoplasm; meta-analysis; oxaliplatin; pharmacogenetic.

Publication types

  • Meta-Analysis

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / ethnology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • DNA-Binding Proteins / genetics
  • Endonucleases / genetics
  • Glutathione S-Transferase pi / genetics
  • Glutathione Transferase / genetics
  • Humans
  • Organoplatinum Compounds / therapeutic use*
  • Oxaliplatin
  • Pharmacogenetics*
  • Xeroderma Pigmentosum Group D Protein / genetics

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Organoplatinum Compounds
  • Oxaliplatin
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • glutathione S-transferase M1
  • ERCC1 protein, human
  • Endonucleases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human