Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

Cordt, B.
Genetic variants in the RAD51, XRCC2 and ERCC2 genes as predictors of outcome in soft tissue sarcoma patients
[ Diplomarbeit ] Medical University of Graz; 2012. pp. 53 [OPEN ACCESS]


Autor*innen der Med Uni Graz:
Gerger Armin
Leithner Andreas
Szkandera Joanna

Background: Soft tissue sarcomas (STS) represent a rare and heterogeneous group of malignant tumours with mesenchymal cell origin and an incidence rate of 3/100.000/year. Despite uniform treatment of the same STS-subtypes we observed some patients to show earlier recurrence and tumour progression. A growing number of studies has been published searching for the link between genetic variabilities like single nucleotide polymorphisms (SNPs) and the varying tumour predisposition. SNPs in DNA-repair genes may alter their function which would be devastating for the integrity of the genome. We investigated the following genes from two of the major DNA-repair pathways, homologous recombination (HR) and nucleotide excision repair (NER): Rad51 rs1801320 G>C, XRCC2 rs3218536 G>A and ERCC2 rs13181 A>C. Patients and methods: For this study 224 patients with histopathologically confirmed soft tissue sarcomas have been recruited at the Department of Orthopaedic Surgery, Medical University of Graz from 1999 till 2010. The relationship between the genotype frequency of the SNPs in patients and clinical factors was assessed by ×2 and Fisher¿s exact probability tests. DFS and OS curves were generated by the Kaplan-Meier method and verified by the log-rank test. Cox¿s proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. Results: In the univariate analysis, the minor allele of ERCC2 rs13181 A>C was significantly associated with increased OS (HR 0.509; 95%CI; 0.289-0.897; p=0.019; Figure 7). Patients carrying at least one C allele in ERCC2 rs13181 A>C showed a median OS of 102 months. In contrast, patients with homozygous A/A had a median OS of 63 months. In multivariate analysis, the ERCC2 rs13181 A>C polymorphism remained significantly associated with increased OS (HR 0.449; 95%CI; 0.241-0.836; p=0.012). Conclusion: Our results indicate an association between ERCC2 rs13181 A>C of the NER-pathway and an increased overall survival for patients with soft tissue sarcoma. It may be due to increased performance of the affected gene caused by structural alteration from a DNA-repair pathway polymorphism.

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