Association of polymorphisms in translesion synthesis genes with prognosis of advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy.

ABSTRACT

BACKGROUND AND OBJECTIVES: Translesion synthesis (TLS) polymerases enable cells to bypass or overcome DNA damage during DNA replication and contributes to genomic instability and cancer. Inhibition of the expression of TLS genes enhances the sensitivity of cancer cells to cisplatin. This study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) in the TLS genes and clinical outcome of advanced non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. METHODS: A total of 16 SNPs were genotyped and analyzed in 302 advanced NSCLC patients (discovery set), and the results were further validated in additional 428 NSCLC patients (validation set). RESULTS: Analyses revealed significant associations of two SNPs, rs3213801 and rs3792136, with overall survival, with the lowest combined P values of 0.003 and 0.016, respectively. These effects also remained in stratification analyses by clinical variables. Furthermore, the number of risk genotypes of the two SNPs showed a cumulative effect on overall survival (P = 0.03). CONCLUSIONS: Genetic polymorphisms in the TLS genes might serve as potential predictive biomarkers of prognosis of advanced NSCLC patients treated with platinum-based chemotherapy.