Influence of DNA repair gene polymorphisms on prognosis in inoperable non‐small cell lung cancer patients treated with radiotherapy and platinum‐based chemotherapy

Abstract

Polymorphisms in DNA repair genes may modulate not only an individual DNA repair capacity, DNA damage levels and cancer risk but also clinical outcome after DNA damage-inducing anticancer therapy. In this study, we analyzed the association between the XPA -4G>A, XPD Asp312Asn, hOGG1 Ser326Cys, XRCC1 Arg399Gln, XRCC2 -4234G>C, XRCC3 -4541A>G and Thr241Met polymorphisms and prognosis in 250 inoperable non-small cell lung cancer (NSCLC) patients treated with radiotherapy and platinum-based chemotherapy. In univariate model, the XPA-4A and XRCC1 399Gln alleles alone and in combination influenced survival only in stage III group. In multivariate analysis, the XPA-4 GA/AA was associated with poor survival (HR 1.55, p = 0.011 overall and HR 1.72, p = 0.008 in stage III). In chemoradiotherapy group, the XPA-4A carriers were at increased risk of death and progression (HR 1.73, p = 0.013 and HR 1.65, p = 0.016, respectively), especially in stage III (p = 0.008). Moreover, individuals with ≥ 2 XPA/XRCC1 adverse alleles showed a higher risk of death (HR 1.46, p = 0.036 overall; HR 1.85, p = 0.004 in stage III and HR 1.71, p = 0.022 in chemoradiotherapy group) and progression (HR 1.75, p = 0.011 overall and HR 1.93, p = 0.005 in stage III). The XPA-4 GA/AA genotype individually and together with the XRCC1 399Gln was an independent unfavorable prognostic factor in our study. Thus, our findings indicate a prognostic potential of the XPA-4G>A in unresected NSCLC treated with radiotherapy and chemoradiotherapy. The results require validation in an independent population.