Association of vascular endothelial growth factor (VEGF) gene polymorphism and increased serum VEGF concentration with pancreatic adenocarcinoma

作者：Sivaprasad Siddapuram^*; Govardhan Bale; Harithakrishna Ramanujam; Rao Guduru Venkat; Pradeep Rebala; Kunal Bharadhwaj; Ramakrishna Nalla; Anuradha Shekaran; Reddy Duvvuru Nageshwar

来源：Pancreatology, 2013, 13(3): 267-272.

DOI：10.1016/j.pan.2013.02.006

• Pancreatic cancer
• Vascular endothelial growth factor (VEGF)
• Angiogenesis
• Single nucleotide polymorphisms (SNPs)
• Genotype-phenotype correlation

Background & aim: Pancreatic cancer is related to high mortality rate. The vascular endothelial growth factor (VEGF) has a strong influence in tumor-related angiogenesis having association with the grade of angiogenesis and the prognosis of different solid tumors including pancreatic cancer. The present study was aimed to analyze the genotype and haplotype distribution of VEGF gene single nucleotide polymorphisms (SNPs), -460T/C, +405G/C, +936C/T, in patients with pancreatic adenocarcinoma from South India, and the effect of these SNPs on serum VEGF level.
Methods: Total 80 patients with pancreatic adenocarcinoma and 87 controls were recruited. The genotype of VEGF gene polymorphisms was determined in both patients and controls using polymerase chain reaction-restriction fragment length polymorphism method. The serum VEGF protein was estimated by standard enzyme-linked immunosorbent assay.
Results: The genotype, +405G/G of VEGF gene showed a significant association with the patients with pancreatic adenocarcinoma (P=0.012, Odds ratio: 2.133), whereas no significant difference was found in the genotype distribution of SNPs, -460C/T and +936C/T between patient and control groups (P>0.05). Serum VEGF level was found to be significantly high in patients (1315.10 pg/Ml, SD +/- 230.79) when compared to controls (591.35 pg/mL, SD +/- 92.48) (P < 0.0001), which showed a strong genotype phenotype correlation between genotype +405G/G and serum VEGF level. Further, the haplotype C-G-T showed a strong association with the disease, and no specific haplotype was associated with increased serum VEGF level.
Conclusion: The polymorphism, +405G/C but not -460T/C and +936C/T, of VEGF gene is strongly associated with pancreatic adenocarcinoma, and this SNP has significant influence on serum VEGF level.

• 出版日期2013-6