title: 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.
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, M Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, 44-101 Gliwice, Poland. dorotab@rocketmail.com
authors.forename: Dorota
authors.initials: D
authors.lastname: Butkiewicz
authors.forename: Anna
authors.initials: A
authors.lastname: Drosik
authors.forename: Rafał
authors.initials: R
authors.lastname: Suwiński
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krześniak
authors.forename: Marek
authors.initials: M
authors.lastname: Rusin
authors.forename: Agata
authors.initials: A
authors.lastname: Kosarewicz
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Rachtan
authors.forename: Iwona
authors.initials: I
authors.lastname: Matuszczyk
authors.forename: Marzena
authors.initials: M
authors.lastname: Gawkowska-Suwińska
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D004260:DNA Repair; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis