title: VEGFR-2, CXCR-2 and PAR-1 germline polymorphisms as predictors of survival in pancreatic carcinoma.
abstract: BACKGROUND
  Hypoxic environment of pancreatic cancer (PC) implicates high vascular in-growth, which may be influenced by angiogenesis-related germline polymorphisms. Our purpose was to evaluate polymorphisms of vascular endothelial growth factor receptor 2 (VEGFR-2), CXC chemokine receptor 2 (CXCR-2), proteinase-activated receptor 1 (PAR-1) and endostatin (ES) as prognostic markers for disease-free (DFS) and overall survival (OS) in PC.
  
  
  METHODS
  Genotyping of 173 patients, surgically treated for PC between 2004 and 2011, was carried out by TaqMan(®) genotyping assays or polymerase chain reaction. Chi-square test, Kaplan-Meier estimator and Cox regression hazard model were used to assess the prognostic value of selected polymorphisms.
  
  
  RESULTS
  VEGFR-2 -906 T/T and PAR-1 -506 Del/Del genotypes predicted longer DFS (P = 0.003, P = 0.014) and OS (VEGFR-2 -906, P = 0.011). CXCR-2 +1208 T/T genotype was a negative predictor for DFS (P < 0.0001). Combined analysis for DFS and OS indicated that patients with the fewest number of favorable genotypes simultaneously present (VEGFR-2 -906 T/T, CXCR-2 +1208 C/T or C/C and PAR-1 -506 Del/Del) were at the highest risk for recurrence or death (P < 0.0001).
  
  
  CONCLUSIONS
  VEGFR-2 -906 C>T, CXCR-2 +1208 C>T and PAR-1 -506 Ins/Del polymorphisms are potential predictors for survival in PC.
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center of Hamburg-Eppendorf, Martinistr. 52, 20246Hamburg, Germany. vashist@uke.de
authors.forename: F G
authors.initials: FG
authors.lastname: Uzunoglu
authors.forename: J
authors.initials: J
authors.lastname: Kolbe
authors.forename: H
authors.initials: H
authors.lastname: Wikman
authors.forename: C
authors.initials: C
authors.lastname: Güngör
authors.forename: B A
authors.initials: BA
authors.lastname: Bohn
authors.forename: M F
authors.initials: MF
authors.lastname: Nentwich
authors.forename: M
authors.initials: M
authors.lastname: Reeh
authors.forename: A M
authors.initials: AM
authors.lastname: König
authors.forename: M
authors.initials: M
authors.lastname: Bockhorn
authors.forename: A
authors.initials: A
authors.lastname: Kutup
authors.forename: O
authors.initials: O
authors.lastname: Mann
authors.forename: J R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Y K
authors.initials: YK
authors.lastname: Vashist
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D020641:Polymorphism, Single Nucleotide; D044463:Receptor, PAR-1 / Q000235:genetics*; D023063:Receptors, Interleukin-8B / Q000235:genetics*; D013534:Survival; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D044463:Receptor, PAR-1; D023063:Receptors, Interleukin-8B; D040301:Vascular Endothelial Growth Factor Receptor-2