title: Influence of vascular endothelial growth factor single nucleotide polymorphisms on tumour development in cutaneous malignant melanoma.
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.
authors.affiliation: Department of Human Genetics, University of Southampton, Southampton, UK. wmh1@soton.ac.uk
authors.forename: W M
authors.initials: WM
authors.lastname: Howell
authors.forename: A C
authors.initials: AC
authors.lastname: Bateman
authors.forename: S J
authors.initials: SJ
authors.lastname: Turner
authors.forename: A
authors.initials: A
authors.lastname: Collins
authors.forename: J M
authors.initials: JM
authors.lastname: Theaker
mesh_terms: D016228:Endothelial Growth Factors / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008222:Lymphokines / Q000235:genetics*; D008545:Melanoma / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D012878:Skin Neoplasms / Q000235:genetics* / Q000503:physiopathology; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors