Prognostic significance of vascular endothelial growth factor gene polymorphisms in patients with colorectal cancer

Int J Clin Oncol. 2013 Dec;18(6):1032-41. doi: 10.1007/s10147-012-0493-6. Epub 2012 Nov 7.

Abstract

Background: Angiogenesis plays an important role in tumor development, progression, and metastasis. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. However, the contribution of common VEGF polymorphisms to colorectal cancer (CRC) prognosis remains unclear.

Methods: We have genotyped four polymorphisms of VEGF (-2578C>A, -1154G>A, -634G>C, and 936C>T) in 350 CRC cases from the Korean population. The genotyping of VEGF polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism assay.

Results: Although not every VEGF polymorphism was significantly correlated with patient prognosis in overall 350 CRC patients, we found that the VEGF -2578CA genotype was associated with a significantly poor prognosis for rectal cancers compared to the CC genotype (HR = 2.156; 95 % CI 1.090-4.267; P = 0.028). In addition, we found that the -2578A/-1154G/-634G/+936C haplotype was significantly associated with a decreased overall survival (OS) rate in all 350 CRC patients (HR = 2.530; 95 % CI 1.340-4.780; P = 0.004). In combination analysis, we found that the combined VEGF -2578CA+AA/-1154GG genotype was associated with a poor OS rate in all 350 CRC patients (HR = 2.068; 95 % CI 1.159-3.693; P = 0.015).

Conclusions: The VEGF gene polymorphisms investigated in this study were not found to be independent prognostic markers in Korean CRC populations. However, our results suggest that the VEGF -2578C>A variant may be a potential genetic marker for rectal cancer prognosis. Further large population studies are warranted to define whether the -2578C>A polymorphism is a prognostic marker of rectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / pathology
  • Polymorphism, Single Nucleotide
  • Prognosis*
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Biomarkers, Tumor
  • Vascular Endothelial Growth Factor A