Influence of DNA repair RAD51 gene variants in overall survival of non-small cell lung cancer patients treated with first line chemotherapy

Cancer Chemother Pharmacol. 2010 Aug;66(3):501-6. doi: 10.1007/s00280-009-1187-2. Epub 2009 Dec 4.

Abstract

Purpose: Lung cancer continues to be the most frequent cancer with approximately one million people worldwide dying of this disease each year. Non-small-cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers. The RAD51 protein is the key protein for homologous recombination, an evolutionarily conserved mechanism for DNA damage repair and the generation of genetic diversity. We conducted this study in order to investigate the effect of the RAD51 G135C polymorphism in treatment response to combined platinum taxanes/gemcitabine first line chemotherapy in NSCLC patients.

Methods: We analysed RAD51 G135C polymorphism in 243 NSCLC patients using PCR-RFLP methodology.

Results: There were no statistically significant differences between the groups of NSCLC patients with the different genotypes regarding tumour stage (p = 0.232). Our results indicate that the mean survival rates were statistically different according to the patient's genotypes. The group of patients carrying the C allele presented a higher mean survival rate than the other patients (56.0 months vs. 41.7 months; p = 0.024). Moreover, regarding smoking history, our results demonstrate that overall survival time differed significantly according to the patient's genotypes in smoker and ex-smoker individuals (p = 0.034). No statistically significant differences were found in the genotype frequencies and overall survival rate among non-smoker NSCLC patients (p = 0.413).

Conclusions: This is the first study evaluating the effect of the RAD51 G135C polymorphism in NSCLC patient survival. Our results suggest that RAD51 genotypes could be useful molecular markers for predicting the clinical outcome of NSCLC patients.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Aged
  • Alleles
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • DNA Repair*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Gemcitabine
  • Genetic Variation
  • Genotype
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Platinum Compounds / administration & dosage
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length
  • Rad51 Recombinase / genetics*
  • Smoking / adverse effects
  • Survival Rate
  • Taxoids / administration & dosage
  • Treatment Outcome

Substances

  • Platinum Compounds
  • Taxoids
  • Deoxycytidine
  • Rad51 Recombinase
  • Gemcitabine