Influence of vascular endothelial growth factor single nucleotide polymorphisms on tumour development in cutaneous malignant melanoma

Genes Immun. 2002 Jun;3(4):229-32. doi: 10.1038/sj.gene.6363851.

Abstract

Vascular endothelial growth factor (VEGF) is a potent regulator of vasculogenesis and tumour angiogenesis. We have investigated whether the VEGF -2578, -1154, +405 and +936 SNPs and associated haplotypes confer susceptibility to and/or influence prognosis in cutaneous malignant melanoma (CMM) skin cancer. A total of 152 CMM patients and 266 controls were genotyped for VEGF promoter SNPs by ARMS-PCR. Strong linkage disequilibrium between the -2578, -1154 and +405 SNPs was detected (association, rho = 0.488-0.965), but not between these SNPs and SNP +936 (association, rho = 0.004-0.130). No SNPs or three SNP haplotypes (-2578, -1154, +405) were significantly associated with CMM, although a number of non-significant trends were observed. However, the VEGF -1154 AA genotype and -2578, -1154, +405 CAC haplotype were both significantly associated with less advanced (Stage 1) disease (P = 0.03). In addition, the VEGF -1154 AA genotype was associated with thinner primary vertical growth phase tumours (P = 0.002), while VEGF -1154 GG was associated with thicker primary tumours (P = 0.02). These preliminary results indicate that VEGF genotype may influence tumour growth in CMM, possibly via the effects of differential VEGF expression on tumour angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endothelial Growth Factors / genetics*
  • Haplotypes
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Linkage Disequilibrium
  • Lymphokines / genetics*
  • Melanoma / genetics*
  • Melanoma / physiopathology
  • Polymorphism, Single Nucleotide*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / physiopathology
  • Survival Analysis
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors