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.

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.

• Authors: F G Uzunoglu, J Kolbe, H Wikman, C Güngör, B A Bohn, M F Nentwich, M Reeh, A M König, M Bockhorn, A Kutup, O Mann, J R Izbicki, Y K Vashist
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 24 Issue 5 Pg. 1282-90 (May 2013) ISSN: 1569-8041 [Electronic] England
• PMID: 23293110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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