Effects of polymorphisms in the XRCC1, XRCC3, and XPG genes on clinical outcomes of platinum-based chemotherapy for treatment of non-small cell lung cancer

Abstract

This study aimed to investigate the effects of single-nucleotide polymorphisms (SNPs) XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPG His104Asp, and XPG His46His in genes involved in the DNA-repair pathway on the outcomes of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). The study period was from January 2005 to January 2006, and 378 NSCLC patients were enrolled within 1 month after being diagnosed with NSCLC. Genomic DNA was extracted using the Qiagen Blood Kit. Polymerase chain reaction combined with a restriction fragment length polymorphism assay was used for genotyping. Individuals with the XRCC1 399A/A genotype had a higher probability of responding well to platinum-based chemotherapy, indicated by an odds ratio (OR) of 2.27 [95% confidence interval (CI) = 1.64-6.97]. Similarly, the XPG T/T genotype was significantly associated with improved responses to chemotherapy, indicated by an OR of 1.90 (95%CI = 1.10-3.28). The XRCC1 399A/A genotype was significantly associated with longer disease-free survival and overall survival, indicated by hazard ratios (HRs) of 0.48 (95%CI = 0.25-0.88) and 0.51 (95%CI = 0.26- 0.98), respectively. Moreover, the XPG 46T/T genotype increased the likelihood of longer disease-free survival and overall survival of NSCLC patients treated with platinum-based chemotherapy (HR = 0.47; 95%CI = 0.22-0.82 and HR = 0.52; 95%CI = 0.31-0.96, respectively). These results indicate that XRCC1 Arg399Gln and XPG His46His might significantly affect the clinical outcomes of platinum-based chemotherapy, highlighting the need for larger studies to confirm the role of these two SNPs in outcomes of NSCLC treatments.