VEGFR-2, CXCR-2 and PAR-1 germline polymorphisms as predictors of survival in pancreatic carcinoma

Ann Oncol. 2013 May;24(5):1282-90. doi: 10.1093/annonc/mds634. Epub 2013 Jan 4.

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.

Patients and 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).

Conclusion: VEGFR-2 -906 C>T, CXCR-2 +1208 C>T and PAR-1 -506 Ins/Del polymorphisms are potential predictors for survival in PC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Disease-Free Survival
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / genetics
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / surgery
  • Polymorphism, Single Nucleotide
  • Receptor, PAR-1 / genetics*
  • Receptors, Interleukin-8B / genetics*
  • Survival
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*

Substances

  • Biomarkers, Tumor
  • Receptor, PAR-1
  • Receptors, Interleukin-8B
  • Vascular Endothelial Growth Factor Receptor-2