Vitamin D receptor gene polymorphisms, serum 25-hydroxyvitamin D levels, and melanoma: UK case-control comparisons and a meta-analysis of published VDR data.

Juliette A Randerson-Moor, John C Taylor, Faye Elliott, Yu-Mei Chang, Samantha Beswick, Kairen Kukalizch, Paul Affleck, Susan Leake, Sue Haynes, Birute Karpavicius, Jerry Marsden, Edwina Gerry, Linda Bale, Chandra Bertram, Helen Field, Julian H Barth, Isabel Dos Santos Silva, Anthony Swerdlow, Peter A Kanetsky, Jennifer H Barrett, D Timothy Bishop, Julia A Newton Bishop

Journal: European journal of cancer (Oxford, England : 1990) 2010;45(18):3271-81

PMID: 19615888

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Abstract

We have carried out melanoma case-control comparisons for six vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) and serum 25-hydroxyvitamin D(3) levels in order to investigate the role of vitamin D in melanoma susceptibility. There was no significant evidence of an association between any VDR SNP and risk in 1028 population-ascertained cases and 402 controls from Leeds, UK. In a second Leeds case-control study (299 cases and 560 controls) the FokI T allele was associated with increased melanoma risk (odds ratio (OR) 1.42, 95% confidence interval (CI) 1.06-1.91, p=0.02). In a meta-analysis in conjunction with published data from other smaller data sets (total 3769 cases and 3636 controls), the FokI T allele was associated with increased melanoma risk (OR 1.19, 95% CI 1.05-1.35), and the BsmI A allele was associated with a reduced risk (OR 0.81, 95% CI 0.72-0.92), in each instance under a parsimonious dominant model. In the first Leeds case-control comparison cases were more likely to have a higher body mass index (BMI) than controls (p=0.007 for linear trend). There was no evidence of a case-control difference in serum 25-hydroxyvitamin D(3) levels. In 1043 incident cases from the first Leeds case-control study, a single estimation of serum 25-hydroxyvitamin D(3) level taken at recruitment was inversely correlated with Breslow thickness (p=0.03 for linear trend). These data provide evidence to support the view that vitamin D and VDR may have a small but potentially important role in melanoma susceptibility, and putatively a greater role in disease progression.

Address: Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS9 7TF, UK.

DOI: 10.1016/j.ejca.2009.06.011

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MeSH Terms: Adolescent, Adult, Aged, Alleles, Body Mass Index, CDX2 Transcription Factor, Case-Control Studies, Deoxyribonucleases, Type II Site-Specific, Female, GATA Transcription Factors, Gene Frequency, Genetic Predisposition to Disease, Hair Color, Homeodomain Proteins, Humans, Male, Melanoma, Middle Aged, Obesity, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Receptors, Calcitriol, Specimen Handling, Statistics as Topic, United Kingdom, Vitamin D, Young Adult