Predictive value of ERCC1 single-nucleotide polymorphism in patients receiving platinum-based chemotherapy for locally-advanced and advanced non-small cell lung cancer--a pilot study

Folia Histochem Cytobiol. 2012 Apr 24;50(1):80-6. doi: 10.2478/18700.

Abstract

Platinum-based chemotherapy is the main type of I-line treatment of advanced and non-operative NSCLC patients without EGFR gene mutation. The excision repair cross-complementation group 1 (ERCC1) is an enzyme that executes the incision of the damaged DNA strand and removes platinum-induced DNA adducts. We investigated whether ERCC1 gene polymorphism has an effect on the response to chemotherapy and survival in 43 patients with NSCLC treated with platinum-based chemotherapy. ERCC1 19007 T>C SNPs were assessed using a PCR-RFLP methods in DNA isolated from peripheral blood lymphocytes. Disease control occurred significantly (p = 0.045) more frequently in patients with CC or CT genotype compared to patients with TT genotype. Median PFS and OS for CC homozygous were 4 and 10.5 months, 4 and 12.5 months for CT heterozygous, but only 0.3 and 1.5 months for TT homozygous patients, respectively. The probability of PFS was significantly higher (HR = 0.438, 95% CI: 0.084-0.881, p = 0.03) and probability of OS was insignificantlyhigher (HR = 0.503, 95% CI: 0.129-1.137, p = 0.084) in patients with CC or CT genotype than in patients with TT genotype. Uncommon TT genotype of ERCC1 19007 T>C polymorphism could predict poor response and shortening of progression free survival in NSCLC patients treated with platinum-based I-line chemotherapy. The analysis of this polymorphism may serve as a promising tool in the qualification of advanced NSCLC patients for appropriate chemotherapy.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Female
  • Genotype
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Organoplatinum Compounds / therapeutic use*
  • Pilot Projects
  • Polymorphism, Single Nucleotide / genetics*
  • Predictive Value of Tests
  • Prognosis

Substances

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