Genetic variants in the vitamin d receptor are associated with advanced prostate cancer at diagnosis: findings from the prostate testing for cancer and treatment study and a systematic review.
Low levels of plasma vitamin D have been implicated as a possible risk factor for both prostate cancer incidence and advanced disease, and recent phase II trials suggest that vitamin D supplementation might delay progression of prostate cancer. Common polymorphisms in the vitamin D receptor (VDR) are associated with VDR activity and are therefore potentially useful proxies for assessing whether vitamin D is causally related to advanced prostate cancer. We genotyped five well-known VDR polymorphisms in 1,604 men with prostate cancer from the Prostate Testing for Cancer and Treatment study. Our aim was to examine the association between VDR polymorphisms and cancer stage (localized versus advanced) as well as cancer grade (Gleason score <7 versus >or=7). Moreover, we also carried out a systematic review and meta-analysis of 13 similar studies. As a result of our meta-analysis, we revealed three polymorphisms, BsmI, ApaI, and TaqI, associated with high Gleason score with an overall summary odds ratios (95% confidence intervals) of 1.12 (1.00-1.25; bb versus BB + Bb), 1.25 (1.02-1.53; aa versus AA + Aa), and 0.82 (0.69-0.98; Tt + tt versus TT), respectively. The haplotype analysis revealed that the BsmI (B)-ApaI (A)-TaqI (t) participants compared with BsmI (b)-ApaI (a)-TaqI (T) individuals were less likely to have high Gleason scores (odds ratio, 0.84; 95% confidence interval, 0.71-1.00; P(unadjusted) = 0.050; P(adjusted) = 0.014). Our finding provides some support for the hypothesis that low levels of vitamin D may increase the risk of prostate cancer progression.
Department of Social Medicine, University of Bristol, Bristol, United Kingdom.
Lina
L
Chen
George
G
Davey Smith
David M
DM
Evans
Angela
A
Cox
Debbie A
DA
Lawlor
Jenny
J
Donovan
Wei
W
Yuan
Ian N M
IN
Day
Richard M
RM
Martin
Athene
A
Lane
Santi
S
Rodriguez
Michael
M
Davis
Luisa
L
Zuccolo
Simon M
SM
Collin
Freddie
F
Hamdy
David
D
Neal
Sarah J
SJ
Lewis
D000368:Aged; D004262:DNA Restriction Enzymes / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
D018167:Receptors, Calcitriol; D004262:DNA Restriction Enzymes