Association of ERCC1-C118T and -C8092A polymorphisms with lung cancer risk and survival of advanced-stage non-small cell lung cancer patients receiving platinum-based chemotherapy: a pooled analysis based on 39 reports

Gene. 2013 Sep 10;526(2):265-74. doi: 10.1016/j.gene.2013.05.021. Epub 2013 May 30.

Abstract

The published data on the predictive role of ERCC1 polymorphisms in lung cancer risk and survival of patients with advanced non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy remains inconsistent. The aim of this meta-analysis was to determine the role of ERCC1 gene polymorphisms (C118T and C8092A) in this clinical situation. Eligible studies were included and assessed for quality using multiple search strategies. Thirty-nine published papers involving 9615 cases (4606 with Stage III/IV disease) and 5542 controls were included in the analysis. Pooled odds ratios (OR) or hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate risk. ERCC1-C118T was associated with lung cancer risk. The OR was 0.90 (95% CI: 0.81-0.99, p=0.043) in an additive genetic model (C allele vs. T allele) and 0.77 (95% CI: 0.63-0.95, p=0.013) in a recessive genetic model (CC/CT vs. TT). The corresponding risk was 0.74 (95% CI: 0.58-0.94, p=0.013) based on a homozygous comparison (CC vs. TT). No significant correlation was found for ERCC1 C8092A and there was no obvious relationship between ERCC1 C118T/C8092A polymorphisms and objective response to platinum-based chemotherapy. Overall survival (OS) of patients with non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy was significantly related to ERCC1 C118T (HR: 1.29, 95% CI: 1.07-1.56, p=0.007, CT/TT vs. CC). There was no relationship between ERCC1 C8092A and survival (HR: 1.32, 95% CI: 0.84-2.10, p=0.23, CA/AA vs. CC). These findings suggest that ERCC1 C118T polymorphisms may serve as a biomarker for lung cancer risk and have prognostic value in patients with advanced non-small cell lung cancer (NSCLC) undergoing platinum-based treatment. Further studies with larger numbers of subjects from a worldwide arena are needed to validate the associations.

Keywords: 95% CI; 95% confidence interval; CR; Chemotherapy; ERCC1; HR; HWE; Hardy–Weinberg equilibrium; Meta-analysis; OR; OS; PD; PR; Platinum; Prognosis; Risk; SD; SNP; complete response; excision repair cross-complementing group 1; hazards ratios; odds ratio; overall survival; partial response; progressive disease; single nucleotide polymorphism; stable disease.

Publication types

  • Meta-Analysis

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Case-Control Studies
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Neoplasm Staging
  • Odds Ratio
  • Platinum / therapeutic use
  • Polymorphism, Single Nucleotide*
  • Publication Bias
  • Risk
  • Treatment Outcome

Substances

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