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The repair of DNA double-strand breaks (DSBs) is the major mechanism to maintain genomic stability in response to irradiation. We hypothesized that genetic polymorphisms in DSB repair genes may affect clinical outcomes among non-small cell lung cancer (NSCLC) patients treated with definitive radio(chemo)therapy. We genotyped six potentially functional single nucleotide polymorphisms (SNPs) (i.e.,  RAD51  −135G>C/rs1801320 and −172G>T/rs1801321,  XRCC2  4234G>C/rs3218384 and R188H/rs3218536 G>A,  XRCC3  T241M/rs861539 and  NBN  E185Q/rs1805794) and estimated their associations with overall survival (OS) and radiation pneumonitis (RP) in 228 NSCLC patients. We found a predictive role of  RAD51  −135G>C SNP in RP development (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.31–0.86,  P  = 0.010 for CG/CC vs. GG). We also found that R AD51  −135G>C and  XRCC2  R188H SNPs were independent prognostic factors for overall survival (adjusted HR = 1.70, 95% CI, 1.14–2.62,  P  = 0.009 for CG/CC vs. GG; and adjusted HR = 1.70; 95% CI, 1.02–2.85,  P  = 0.043 for AG vs. GG, respectively) and that the SNP-survival association was most pronounced in the presence of RP. Our study suggests that HR genetic polymorphisms, particularly  RAD51  −135G>C, may influence overall survival and radiation pneumonitis in NSCLC patients treated with definitive radio(chemo)therapy. Large studies are needed to confirm our findings.

Polymorphisms of Homologous Recombination Genes and Clinical Outcomes of Non-Small Cell Lung Cancer Patients Treated with Definitive Radiotherapy