A meta-analysis identifies ERCC1 gene polymorphism as a predictor of better patient response to treatment with radiochemotherapy

Cancer Chemother Pharmacol. 2016 Jun;77(6):1183-91. doi: 10.1007/s00280-016-3015-9. Epub 2016 Apr 21.

Abstract

Purpose: This meta-analysis aimed to evaluate whether an association exists between the ERCC1 rs11615 (C>T) polymorphism and patient response to platinum-based chemotherapy and radiation-based chemotherapy.

Methods: Publications were selected from PubMed and MEDLINE. A meta-analysis was conducted to determine the association between genetic polymorphisms and response to platinum-based chemotherapy and radiation-based chemotherapy by checking the odds ratios (ORs) and 95 % confidence intervals (CIs).

Results: In our overall analysis, the ERCC1 rs11615 (C>T) polymorphism was not associated with response to platinum-based chemotherapy in five comparison models. In the subgroup analyses by ethnicity, the ERCC1 rs11615 (C>T) polymorphism was shown to be significantly associated with objective response in Caucasian patients treated with platinum-based chemotherapy in the recessive model (TT vs.

Ct/cc: OR 0.696, 95 % CI 0.508-0.954, heterogeneity = 0.330), but the association was not observed in the Asian population. The C allele was significantly associated with better response to radiochemotherapy in the recessive model comparison (TT vs.

Cc/ct: OR 0.724, 95 % CI 0.585-0.869, heterogeneity = 0.008). Subgroup analysis by cancer type revealed that the C allele of ERCC1 rs11615 predicted a better response in esophageal cancers in two comparison models (T vs. C: OR 0.756, 95 % CI 0.648-0.880, heterogeneity = 0.653; TT vs.

Tc/cc: OR 0.457, 95 % CI 0.306-0.684, heterogeneity = 0.723). Stratified analysis by ethnicity showed a better response in Caucasians in allelic comparison model (T vs. C: OR 0.895, 95 % CI 0.819-0.977, heterogeneity = 0.095).

Conclusion: Together, our results suggest that the ERCC1 rs11615 (C>T) polymorphism was associated with therapeutic response in Caucasian patients and C allele of ERCC1 rs11615 could represent a genetic molecular marker to predict better patient response to radiochemotherapy in recessive model. However, larger prospective randomized trials will be required.

Keywords: ERCC1; Meta-analysis; Platinum-based chemotherapy; Polymorphism; Radiochemotherapy.

Publication types

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

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use
  • Chemoradiotherapy / methods*
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Genetic Markers / genetics
  • Humans
  • Neoplasms / genetics
  • Neoplasms / therapy*
  • Odds Ratio
  • Platinum / administration & dosage
  • Platinum / therapeutic use
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • Treatment Outcome
  • White People / genetics*

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Genetic Markers
  • Platinum
  • ERCC1 protein, human
  • Endonucleases