No association between XRCC1 polymorphisms and survival in non-small-cell lung cancer patients treated with platinum-based chemotherapy

Cancer Biol Ther. 2010 Nov 1;10(9):854-9. doi: 10.4161/cbt.10.9.13238. Epub 2010 Nov 1.

Abstract

Purpose: genetic polymorphisms in DNA repair genes are thought to represent important determinants of platinum drug efficacy. The current study investigated whether single nucleotide polymorphisms (SNPs) in the X-ray repair cross complementing protein 1 (XRCC1) gene are associated with survival in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.

Experimental design: a total of 199 platinum-treated patients with stage III-IV NSCLC were recruited. Overall survival (OS) and progression-free survival (PFS) according to genotypes and haplotypes were analyzed using Kaplan-Meier method and assessed by log-rank test. Hazard ratios (HRs) were calculated using Cox proportional hazards models by adjusting for clinical factors.

Results: during the median 26.5 months of follow-up, 159 deaths occurred. Regarding XRCC1 Arg194Trp, Arg280His, and Arg399Gln genotypes, no significant effects on survival were observed, although the 280Arg/His genotype was associated with a borderline-significant higher median survival time (20.0 months for Arg/His versus 16.0 months for Arg/Arg; P = 0.131). Moreover, no significant association of haplotypes with survival was found.

Conclusions: this study showed no influence of the XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphisms on survival in advanced NSCLC patients with platinum-based chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics*
  • Disease-Free Survival
  • Female
  • Genotype
  • Haplotypes
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Platinum Compounds / therapeutic use*
  • Polymorphism, Single Nucleotide*
  • Proportional Hazards Models
  • Survival Rate
  • X-ray Repair Cross Complementing Protein 1

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Platinum Compounds
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human