Comprehensive analysis of DNA repair gene polymorphisms and survival in patients with early stage non-small-cell lung cancer

Cancer Sci. 2010 Nov;101(11):2436-42. doi: 10.1111/j.1349-7006.2010.01699.x.

Abstract

This study was conducted to analyze a comprehensive panel of single nucleotide polymorphisms (SNP) in DNA repair genes to determine the relationship between polymorphisms and the survival outcome of patients with early stage non-small-cell lung cancer (NSCLC). Three hundred and ten consecutive patients with surgically resected NSCLC were enrolled. Forty-eight SNP in 27 DNA repair genes were genotyped and their associations with overall survival (OS) and disease-free survival (DFS) were analyzed. Individually, six SNP exhibited significant associations with survival outcome. When the six SNP were combined, OS and DFS decreased as the number of bad genotypes increased (P(trend) <0.0001 for both). Patients with three, and four or five bad genotypes had a significantly worse OS and DFS compared with those carrying zero or one bad genotypes (adjusted hazard ratio [aHR] for OS=3.53, 95% confidence interval [CI]=1.25-9.97, P=0.02, and aHR for DFS=3.31, 95% CI=1.41-7.76, P=0.006; and aHR for OS=5.47, 95% CI=1.87-16.00, P=0.002, and aHR for DFS=4.42, 95% CI=1.82-10.74, P=0.001, respectively). These findings suggest that the six SNP identified can be used as prognostic markers for patients with surgically resected early stage NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • DNA Modification Methylases / genetics
  • DNA Repair / genetics*
  • DNA Repair Enzymes / genetics
  • DNA-Binding Proteins / genetics
  • Disease-Free Survival
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • MutS Homolog 2 Protein / genetics
  • Neoplasm Staging
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / genetics
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Tumor Suppressor Proteins / genetics
  • X-ray Repair Cross Complementing Protein 1
  • Xeroderma Pigmentosum Group D Protein / genetics

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XPC protein, human
  • DNA Modification Methylases
  • MGMT protein, human
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • MSH2 protein, human
  • MutS Homolog 2 Protein
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • DNA Repair Enzymes