Common gene variants in RAD51, XRCC2 and XPD are not associated with clinical outcome in soft-tissue sarcoma patients

Cancer Epidemiol. 2013 Dec;37(6):1003-9. doi: 10.1016/j.canep.2013.10.003. Epub 2013 Nov 2.

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.

Conclusion: 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.

Keywords: Gene variant; Homologous recombination; Nucleotide excision repair; Soft-tissue sarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Combined Modality Therapy
  • DNA Repair
  • DNA, Neoplasm / genetics
  • DNA-Binding Proteins / genetics*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Rad51 Recombinase / genetics*
  • Retrospective Studies
  • Sarcoma / genetics*
  • Sarcoma / mortality
  • Sarcoma / therapy
  • Survival Rate
  • Xeroderma Pigmentosum Group D Protein / genetics*
  • Young Adult

Substances

  • DNA, Neoplasm
  • DNA-Binding Proteins
  • XRCC2 protein, human
  • RAD51 protein, human
  • Rad51 Recombinase
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human