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

British Journal of Cancer
J A HalsallP E Hutchinson

Abstract

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 eff...Continue Reading

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