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Common gene variants in RAD51, XRCC2 and XPD are not associated with clinical outcome in soft-tissue sarcoma patients
Authors:Joanna Szkandera  Gudrun Absenger  Bernadette Liegl-Atzwanger  Martin Pichler  Michael Stotz  Stefan Gerger  Maximilian Zacherl  Wilfried Renner  Miao Haijun  Andreas Leithner  Armin Gerger
Affiliation:1. Division of Clinical Oncology, Research Unit Genetic Epidemiology and Pharmacogenetics, Department of Medicine, Medical University of Graz, Graz, Austria;2. Institute of Pathology, Medical University of Graz, Graz, Austria;3. Department of Orthopaedic Surgery, Medical University of Graz, Graz, Austria;4. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
Abstract:BackgroundDNA repair mechanisms play a major role in cancer risk and progression. Germline variants in DNA repair genes may result in altered gene function and/or activity, thereby causing inter-individual differences in a patient's tumor recurrence capacity. In genes of the DNA repair pathway the gene variants RAD51 rs1801320 G > C, XRCC2 rs3218536 G > A and XPD rs13181 A > C have been previously related to genetic predisposition and prognosis of various cancer entities. In this study we investigated the association between these polymorphisms and time to recurrence (TTR) and overall survival (OS) in soft-tissue sarcoma (STS) patients after curative surgery.MethodsTwo hundred sixty STS patients were included in this retrospective study. Germline DNA was genotyped by 5′-exonuclease (TaqMan) technology. Kaplan Meier curves and multivariate Cox proportional models were calculated for TTR and OS.ResultsA statistically significant association was observed between tumor grade and adjuvant radiotherapy and TTR and between tumor grade and OS. No association was found between RAD51 rs1801320 G > C, XRCC2 rs3218536 G > A and XPD rs13181 A > C and TTR and OS in univariate and multivariate analysis.ConclusionOur results underline a prognostic effect of tumor grade and adjuvant radiotherapy in STS patients but indicate no association between RAD51 rs1801320 G > C, XRCC2 rs3218536 G > A and XPD rs13181 A > C and clinical outcome in STS patients after curative surgery.
Keywords:Gene variant  Nucleotide excision repair  Homologous recombination  Soft-tissue sarcoma
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