The ERCC1 C118T polymorphism predicts clinical outcomes of colorectal cancer patients receiving oxaliplatin-based chemotherapy: a meta-analysis based on 22 studies

Asian Pac J Cancer Prev. 2014;15(19):8383-90. doi: 10.7314/apjcp.2014.15.19.8383.

Abstract

Background: Although the predictive value of the excision repair cross-complementing group 1 (ERCC1) C118T polymorphism in clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, the conclusions are conflicting. Therefore, we performed the present meta-analysis to determine the precise role of the ERCC1 C118T polymorphism in this clinical situation and help optimize individual chemotherapy.

Materials and methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate objective response and oxaliplatin-induced toxicity, with hazard ratios (HRs) with 95%CIs for progression-free survival (PFS) and overall survival (OS).

Results: A total of 22 studies including 2,846 CRC patients were eligible in the analysis. Overall, no significant correlation was found between the ERCC1 C118T polymorphism and objective response to oxaliplatin-based chemotherapy, in all patients or in the Asian and Caucasian subgroups. However, the pooled analysis showed that the PFS and OS were significantly shorter in patients who carried T/T or T/C genotypes of ERCC1 C118T as compared to the C/C genotype. On stratified analysis by ethnicity, the ERCC1 118T allele was associated with a favorable prognosis in Caucasians (PFS, HR=0.58, 95%CI: 0.24-1.44; OS, HR=0.38, 95%CI: 0.22-0.64) but an unfavorable prognosis in Asians (PFS, HR=2.49, 95%CI: 1.87-3.33; OS, HR=2.63, 95%CI: 1.87-3.69) based on a dominant model. In addition, we failed to find a statistically significant impact of ERCC1 C118T polymorphism on oxaliplatin-induced toxicity.

Conclusions: The ERCC1 C118T polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.

Publication types

  • Meta-Analysis

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Humans
  • Organoplatinum Compounds / therapeutic use*
  • Oxaliplatin
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Risk Factors
  • Survival Rate

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Organoplatinum Compounds
  • Oxaliplatin
  • ERCC1 protein, human
  • Endonucleases