A novel polymorphism in the 1A promoter region of the vitamin D receptor is associated with altered susceptibilty and prognosis in malignant melanoma

J A Halsall, J E Osborne, L Potter, J H Pringle, P E Hutchinson

Research output: Contribution to journalArticlepeer-review

82 Citations (Scopus)


The association of Taq 1 and Fok 1 restriction fragment length polymorphisms of the vitamin D receptor with occurrence and outcome of malignant melanoma (MM), as predicted by tumour (Breslow) thickness, has been reported previously. We now report a novel adenine-guanine substitution -1012 bp relative to the exon 1a transcription start site (A-1012G), found following screening by single-stranded conformational polymorphism of this promoter region. There was a total of 191 MM cases, which were stratified according to conventional Breslow thickness groups, cases being randomly selected from each group to form a distribution corresponding to the known distribution of Breslow thickness in our area, and this population (n=176) was compared to 80 controls. The A allele was over-represented in MM patients and, with GG as reference, odds ratio (OR) for AG was 2.5, 95% confidence interval (CI) 1.1-5.7, (P=0.03) and AA 3.3, CI 1.4-8.1, (P=0.007). The outcome was known in 171 of 191 patients and the A allele was related to the development of metastasis, the Kaplan-Meier estimates of the probability of metastasis at 5 years being: GG 0%; AG 9%, CI 4-16%; AA 21%, CI 12-36%; (P=0.008), and to thicker Breslow thickness groups (P=0.04). The effect on metastasis was independent of tumour thickness and A-1012G may have predictive potential, additional to Breslow thickness. Neither the Fok 1 nor Taq 1 variants (f and t) were significantly related to the development of metastasis, although there was a strong relationship of fftt with the thickest Breslow thickness group (P=0.005). There was an interaction between the A-1012G and Fok 1 polymorphisms (P=0.025) and the Fok 1 variant enhanced the effect of the A allele of the A-1012G polymorphism on metastasis, the probability of metastasis for AAff at 5 years follow-up being 57%, CI 24-92%.

Original languageEnglish
Pages (from-to)765-70
Number of pages6
JournalBritish Journal of Cancer
Issue number4
Publication statusPublished - 16 Aug 2004


  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Melanoma
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Odds Ratio
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Polymorphism, Single-Stranded Conformational
  • Prognosis
  • Promoter Regions, Genetic
  • Receptors, Calcitriol
  • Skin Neoplasms
  • Survival Analysis


Dive into the research topics of 'A novel polymorphism in the 1A promoter region of the vitamin D receptor is associated with altered susceptibilty and prognosis in malignant melanoma'. Together they form a unique fingerprint.

Cite this