title: Association between single nucleotide polymorphisms in the gene for XRCC1 and radiation-induced late toxicity in prostate cancer patients.
abstract: OBJECTIVE
  Polymorphisms in genes responsible for DNA damage signaling and repair might modulate DNA repair capacity and, therefore, affect cell and tissue response to radiation and influence individual radiosensitivity. The purpose of the present prospective investigation was to evaluate the association of single nucleotide polymorphisms in XRCC1 with radiation-induced late side effects in prostate cancer patients treated with radiotherapy.
  
  
  METHODS
  To analyze the role of XRCC1 polymorphisms for late toxicity 603 participants from the Austrian PROCAGENE study treated with three-dimensional conformal radiotherapy were included in the present investigation. Three non-synonymous candidate polymorphisms in the X-ray repair cross-complementing group 1 (XRCC1) gene (Arg194Trp; Arg280His; Arg399Gln) were selected and determined by 5´-nuclease (TaqMan) assays.
  
  
  RESULTS
  Within a median follow-up time of 35 months, 91 patients (15.7%) developed high-grade late toxicities (defined as late bladder and/or rectal toxicity RTOG≥2). In a Kaplan-Meier analysis, carriers of the XRCC1 Arg280His polymorphism were at decreased risk of high-grade late toxicity (p=0.022), in multivariate analysis including clinical and dosimetric parameters as potential confounders the XRCC1 Arg280His polymorphism remained a significant predictor for high-grade late toxicity (HR=0.221, 95% CI 0.051-0.956; p=0.043). No significant associations were found for the remaining polymorphisms.
  
  
  CONCLUSIONS
  We conclude that the XRCC1 Arg280His polymorphism may be protective against the development of high-grade late toxicity after radiotherapy in prostate cancer patients.
authors.affiliation: Department of Therapeutic Radiology and Oncology, Medical University of Graz, Auenbruggerplatz 32, Graz, Austria. tanja.langsenlehner@klinikum-graz.at
authors.forename: Tanja
authors.initials: T
authors.lastname: Langsenlehner
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.forename: Armin
authors.initials: A
authors.lastname: Gerger
authors.forename: Günter
authors.initials: G
authors.lastname: Hofmann
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Thurner
authors.forename: Karin S
authors.initials: KS
authors.lastname: Kapp
authors.forename: Uwe
authors.initials: U
authors.lastname: Langsenlehner
mesh_terms: D001317:Austria; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000235:genetics*; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D012007:Rectum / Q000528:radiation effects; D013997:Time Factors; D001743:Urinary Bladder / Q000528:radiation effects; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human