Polymorphisms in ERCC1 gene could predict clinical outcome of platinum-based chemotherapy for non-small cell lung cancer patients

Tumour Biol. 2014 Aug;35(8):8335-41. doi: 10.1007/s13277-014-2033-7. Epub 2014 May 24.

Abstract

We analyzed the role of three common single-nucleotide polymorphisms (SNPs) of ERCC1 in predicting the tumor responses and the survival of non-small cell lung cancer (NSCLC) patients who received platinum-based chemotherapy. One hundred ninety-two patients who were identified as stage IV or IIIB/A NSCLC were collected between January 2008 and December 2009. ERCC1 rs11615, rs3212986, and rs2298881 were selected and genotyped by MassARRAY® Analyzer 4 system. One hundred three (53.65 %) patients showed a CR and PR to chemotherapy, and 81 (42.19 %) patients died from NSCLC with the median OS of 35.82 ± 15.19 months. Multivariate regression analysis showed that rs11615 TT genotype and T allele were associated with optimal response to chemotherapy, and rs3212986 AA and A allele were correlated with better response to chemotherapy. Cox regression showed that patients carrying the rs11615 TT genotype and T allele and the rs3212986 AA genotype and A allele were significantly associated with higher risk of death from NSCLC. In conclusion, ERCC1 rs11615 and rs3212986 polymorphism were associated with a poor response to chemotherapy and shorter survival time of advanced NSCLC. ERCC1 rs11615 and rs3212986 polymorphisms may be helpful for designing individualized cancer treatment for NSCLC patients.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Platinum / therapeutic use
  • Polymorphism, Genetic*
  • Proportional Hazards Models

Substances

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