Assessment of XPD Lys751Gln and XRCC1 T-77C polymorphisms in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy

Lung Cancer. 2011 Jul;73(1):110-5. doi: 10.1016/j.lungcan.2010.11.004. Epub 2010 Dec 3.

Abstract

Polymorphisms in DNA repair genes were thought to represent important determinants of platinum drug efficacy. This study tested whether XPD Lys751Gln and XRCC1 T-77C polymorphisms were associated with survival in platinum-treated patients with advanced non-small-cell lung cancer (NSCLC). In this study, 199 advanced NSCLC patients with platinum-based chemotherapy were recruited. During the median 26.5 months of follow-up, patients with the XPD 751Lys/Lys genotype had a median survival time of 17.0 months (95% CI, 14.5-19.6 months), not much longer than those carried Lys/Gln heterozygote (12.0 months; 95% CI, 3.4-20.6 months; log-rank test, P=0.542). In Cox proportional hazards model, no significant associations were found between XPD Lys751Gln polymorphism and survival. For XRCC1 T-77C polymorphism, the median survival of patients with TC+CC genotype (18 months; 95% CI, 13.5-22.5 months) was similar to those with the TT genotype (16.0 months; 95% CI, 13.3-18.7 months; log-rank test, P=0.399). XRCC1 T-77C polymorphism was not associated with survival in Cox proportional hazards model. Additionally, the analysis for combination of these two polymorphisms also showed no prognostic significance for NSCLC. Our findings indicated that neither XPD Lys751Gln nor XRCC1 T-77C could be genetic determinant for prognosis of advanced NSCLC patients treated with platinum-based chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bridged-Ring Compounds / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Cisplatin / administration & dosage
  • DNA-Binding Proteins / genetics*
  • Disease-Free Survival
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Taxoids / administration & dosage
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives
  • Vinorelbine
  • X-ray Repair Cross Complementing Protein 1
  • Xeroderma Pigmentosum Group D Protein / genetics*

Substances

  • Bridged-Ring Compounds
  • DNA-Binding Proteins
  • Organoplatinum Compounds
  • Taxoids
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Oxaliplatin
  • taxane
  • Vinblastine
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • Cisplatin
  • Vinorelbine