Vitamin D receptor gene polymorphisms, serum 25-hydroxyvitamin D levels, and melanoma: UK case-control comparisons and a meta-analysis of published VDR data.
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.
Randerson-Moor
Juliette A
JA
Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS9 7TF, UK.
Taylor
John C
JC
Elliott
Faye
F
Chang
Yu-Mei
YM
Beswick
Samantha
S
Kukalizch
Kairen
K
Affleck
Paul
P
Leake
Susan
S
Haynes
Sue
S
Karpavicius
Birute
B
Marsden
Jerry
J
Gerry
Edwina
E
Bale
Linda
L
Bertram
Chandra
C
Field
Helen
H
Barth
Julian H
JH
Silva
Isabel Dos Santos
Idos S
Swerdlow
Anthony
A
Kanetsky
Peter A
PA
Barrett
Jennifer H
JH
Bishop
D Timothy
DT
Bishop
Julia A Newton
JA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D000071616:CDX2 Transcription Factor; D016022:Case-Control Studies; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D005260:Female; D050980:GATA Transcription Factors / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006200:Hair Color / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D013048:Specimen Handling; D013223:Statistics as Topic; D006113:United Kingdom; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D055815:Young Adult
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D050980:GATA Transcription Factors; D018398:Homeodomain Proteins; D018167:Receptors, Calcitriol; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D015252:Deoxyribonucleases, Type II Site-Specific