¹Department of Human Genetics, University of Southampton, Southampton, UK

²Histocompatibility and Immunogenetics Laboratory, Southampton General Hospital, Southampton, UK

³Department of Cellular Pathology, Southampton General Hospital, Southampton, UK

Correspondence to: Dr W M Howell, Histocompatibility and Immunogenetics Laboratory, Tenovus Building, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. E-mail: wmh1@soton.ac.uk

This work was supported by a grant from the Association for International Cancer Research, St Andrews, Scotland (No. 99-121)

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, = 0.488-0.965), but not between these SNPs and SNP +936 (association, = 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.

Genes and Immunity (2002) 3, 229-232. doi:10.1038/sj.gene.6363851

VEGF; SNPs; angiogenesis; malignant melanoma; cancer