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

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Correspondence to W M Howell.

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

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Howell, W., Bateman, A., Turner, S. et al. Influence of vascular endothelial growth factor single nucleotide polymorphisms on tumour development in cutaneous malignant melanoma. Genes Immun 3, 229–232 (2002). https://doi.org/10.1038/sj.gene.6363851

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