Predictive effects of ERCC1 and XRCC3 SNP on efficacy of platinum-based chemotherapy in advanced NSCLC patients

Jpn J Clin Oncol. 2010 Oct;40(10):954-60. doi: 10.1093/jjco/hyq071. Epub 2010 May 12.

Abstract

Objective: The purpose of the study was to investigate whether single-nucleotide polymorphisms of deoxyribonucleic acid repair gene excision repair cross-complementing group 1 at codon 118 and X-ray repair cross-complementing group 3 at codon 241 affected clinical outcomes in advanced non-small cell lung cancer patients receiving first-line platinum-based chemotherapy.

Methods: A total of 130 patients treated with platinum-based doublets were examined for genotyping of excision repair cross-complementing group 1 118 and X-ray repair cross-complementing group 3 241 in peripheral blood lymphocytes with the method of the TaqMan assay plus the real-time polymerase chain reaction method. Multivariate logistic or Cox's regression analyses were used to adjust for possible confounding variables.

Results: There were no differences in clinical characteristics among the different single-nucleotide polymorphisms. Overall response rate in the 130 patients was 20% with 85.4% of disease control rate. Followed up to 31 March 2008, there were 47 patients still alive. Overall survival was 15 months. No relationship was found between excision repair cross-complementing group 1 or X-ray repair cross-complementing group 3 single-nucleotide polymorphisms and tumor response to platinum-based chemotherapy. A significant correlation was found between excision repair cross-complementing group 1 118 C/T single-nucleotide polymorphisms and survival (P = 0.003). In the multivariate model, the survival was highly related with excision repair cross-complementing group 1 118 C/T or T/T genotypes and tumor response to chemotherapy.

Conclusions: Overall survival was significantly improved in the patients with excision repair cross-complementing group 1 118 T/T or C/T treated by platinum-based chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Base Sequence
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cisplatin / administration & dosage
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Regression Analysis
  • Treatment Outcome

Substances

  • DNA-Binding Proteins
  • X-ray repair cross complementing protein 3
  • Carboplatin
  • ERCC1 protein, human
  • Endonucleases
  • Cisplatin