title: The Glu228Ala polymorphism in the ligand binding domain of death receptor 4 is associated with increased risk for prostate cancer metastases.
abstract: BACKGROUND
  Death receptor 4, encoded by the TNFRSF10A gene, is an important mediator of apoptosis and its dysfunction may be related to cancer development and distant tumor spread. A single nucleotide polymorphism in TNFRSF10A (Glu228Ala, rs20576) within a conserved region of the extracellular cysteine-rich domain of death receptor 4 has been associated with an increased risk for a variety of tumor entities. Aim of the present study was to evaluate the role of the TNFRSF10A polymorphism in metastatic progression of prostate cancer after radiation therapy.
  
  
  METHODS
  We carried out a prospective study including 702 prostate cancer patients from the Austrian PROCAGENE (Prostate Cancer Genetics) study. Development of metastases was examined in regular follow-up investigations. TNFRSF10A genotypes were determined by a 5'-nuclease assay (TaqMan).
  
  
  RESULTS
  Within a median follow-up time of 10 months (range 0-60 months), 24 (3.4%) patients developed metastases. In a Cox regression model including age at diagnosis and risk group as potential confounders, carriage of an 228Ala allele was associated with a relative risk of 2.47 (95% CI 1.10-5.54; P=0.028) for metastases. TNFRSF10A genotypes were not associated with tumor stage, grade, risk group or age at diagnosis.
  
  
  CONCLUSIONS
  We conclude that the TNFRSF10A Glu228Ala polymorphism may be a novel independent risk factor for prostate cancer metastases after radiation therapy.
authors.affiliation: Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz, Austria. tanya.langsenlehner@klinikum-graz.at
authors.forename: Tanja
authors.initials: T
authors.lastname: Langsenlehner
authors.forename: Uwe
authors.initials: U
authors.lastname: Langsenlehner
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.forename: Karin S
authors.initials: KS
authors.lastname: Kapp
authors.forename: Peter
authors.initials: P
authors.lastname: Krippl
authors.forename: Günter
authors.initials: G
authors.lastname: Hofmann
authors.forename: Heimo
authors.initials: H
authors.lastname: Clar
authors.forename: Karl
authors.initials: K
authors.lastname: Pummer
authors.forename: Ramona
authors.initials: R
authors.lastname: Mayer
mesh_terms: D000368:Aged; D001317:Austria; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008024:Ligands; D008297:Male; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D017434:Protein Structure, Tertiary; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D008024:Ligands; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C105190:TNFRSF10A protein, human