Genetic variability of ERCC1 genes in NER pathway influences the treatment outcome of gastric cancer

Int J Clin Exp Pathol. 2015 Oct 1;8(10):13367-73. eCollection 2015.

Abstract

We conducted a prospective study to analyze whether six SNPs in ERCC1 gene could serve as potential biomarkers for prognosis of gastric cancer. Between January 2010 and December 2012, 270 patients with pathologically proven gastric cancer and receiving platinum-based chemotherapy were recruited in our study. Genotyping of the ERCC1 rs11615, rs2298881, rs3212955, rs3212961, rs3212986 and rs735482 were carried out using the Sequenom MassARRAY platform. By logistic regression analysis, patients carrying the GT and TT genotypes of rs3212986 showed a significantly poorer response to chemotherapy than did those carrying the GG genotype, and the ORs (95% CI) were 0.47 (0.25-0.88) and 0.18 (0.08-0.41), respectively. By Cox proportional hazards models, the GT and TT genotypes of rs3212986 were correlated with increased risk of death when compared with the GG genotype, and the adjusted HRs (95% CIs) were 1.79 (1.01-3.16) and 2.57 (1.18-5.62), respectively. However, we did not find significant association between ERCC1 rs11615, rs2298881, rs3212955, rs3212961 and rs735482 and response to chemotherapy and overall survival in patients with gastric cancer. In conclusion, the results of the present retrospective study indicate that there is a significant difference in biological behavior between ERCC1 rs3212986 gene polymorphism and treatment outcome of gastric cancer.

Keywords: ERCC1; gastric cancer; polymorphism; treatment outcome.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • DNA Repair / genetics*
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • ERCC1 protein, human
  • Endonucleases