title: Impact of VEGF gene polymorphisms and haplotypes on radiation-induced late toxicity in prostate cancer patients.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF) is an important determinant of microvascular permeability and angiogenesis and has been shown to be up-regulated during the late phase of radiation injury. The present prospective study was performed to evaluate the role of VEGF gene polymorphisms and haplotypes in the development of radiation-induced late side effects in prostate cancer patients.
  
  
  METHODS
  The association of VEGF gene polymorphisms and haplotypes with high-grade late rectal or urinary toxicity (defined as late toxicity EORTC/RTOG ≥ 2) was analyzed using 493 prostate cancer patients from the Austrian PROCAGENE study treated with definitive radiotherapy. Seven candidate polymorphisms in the VEGF gene were selected and determined by 5'-nuclease (TaqMan) assays.
  
  
  RESULTS
  Within a median follow-up time of 48 months, 42 patients (8.6%) developed high-grade late rectal and 47 patients (9.6%) urinary toxicity, respectively. In a Kaplan-Meier analysis, carriers of the VEGF -7C > T polymorphism were at increased risk of high-grade late rectal toxicity (p = 0.003) and in a multivariate analysis including clinical and dosimetric parameters as potential confounders the VEGF -7C > T polymorphism remained a significant predictor (HR = 2.8, 95% CI 1.349-5.813; p = 0.006). Furthermore, the ATTGT haplotype formed by five polymorphisms upstream of the coding sequence demonstrated a significant association with late rectal toxicity grade ≥ 2 (p = 0.001). No significant associations were found for the remaining polymorphisms and haplotypes.
  
  
  CONCLUSIONS
  We conclude that genetic variants in the VEGF gene may influence the risk of high-grade late rectal toxicity after definitive radiotherapy for prostate cancer.
authors: Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz, Austria. tanja.langsenlehner@klinikum-graz.at
authors: Tanja
authors: T
authors: Langsenlehner
authors: Wilfried
authors: W
authors: Renner
authors: Armin
authors: A
authors: Gerger
authors: Günter
authors: G
authors: Hofmann
authors: Eva-Maria
authors: EM
authors: Thurner
authors: Karin S
authors: KS
authors: Kapp
authors: Uwe
authors: U
authors: Langsenlehner
mesh_terms: D000368:Aged; D000483:Alleles; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000235:genetics*; D012007:Rectum / Q000528:radiation effects*; D001743:Urinary Bladder / Q000528:radiation effects*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A