title: Common gene variants in RAD51, XRCC2 and XPD are not associated with clinical outcome in soft-tissue sarcoma patients.
abstract: BACKGROUND
  DNA 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.
  
  
  METHODS
  Two 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Division of Clinical Oncology, Research Unit Genetic Epidemiology and Pharmacogenetics, Department of Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Joanna
authors.initials: J
authors.lastname: Szkandera
authors.forename: Gudrun
authors.initials: G
authors.lastname: Absenger
authors.forename: Bernadette
authors.initials: B
authors.lastname: Liegl-Atzwanger
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
authors.forename: Michael
authors.initials: M
authors.lastname: Stotz
authors.forename: Stefan
authors.initials: S
authors.lastname: Gerger
authors.forename: Maximilian
authors.initials: M
authors.lastname: Zacherl
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.forename: Miao
authors.initials: M
authors.lastname: Haijun
authors.forename: Andreas
authors.initials: A
authors.lastname: Leithner
authors.forename: Armin
authors.initials: A
authors.lastname: Gerger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D051135:Rad51 Recombinase / Q000235:genetics*; D012189:Retrospective Studies; D012509:Sarcoma / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D015996:Survival Rate; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C113187:XRCC2 protein, human; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
keywords: Gene variant; Homologous recombination; Nucleotide excision repair; Soft-tissue sarcoma