Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis.
BACKGROUND
Disturbed folate metabolism is associated with an increased risk of some cancers. Our objective was to determine whether blood levels of folate, vitamin B(12), and related metabolites were associated with prostate cancer risk.


METHODS
Matched case-control study nested within the U.K. population-based Prostate testing for cancer and Treatment (ProtecT) study of prostate-specific antigen-detected prostate cancer in men ages 50 to 69 years. Plasma concentrations of folate, B(12) (cobalamin), holo-haptocorrin, holo-transcobalamin total transcobalamin, and total homocysteine (tHcy) were measured in 1,461 cases and 1,507 controls. ProtecT study estimates for associations of folate, B(12), and tHcy with prostate cancer risk were included in a meta-analysis, based on a systematic review.


RESULTS
In the ProtecT study, increased B(12) and holo-haptocorrin concentrations showed positive associations with prostate cancer risk [highest versus lowest quartile of B(12) odds ratio (OR) = 1.17 (95% confidence interval, 0.95-1.43); P(trend) = 0.06; highest versus lowest quartile of holo-haptocorrin OR = 1.27 (1.04-1.56); P(trend) = 0.01]; folate, holo-transcobalamin, and tHcy were not associated with prostate cancer risk. In the meta-analysis, circulating B(12) levels were associated with an increased prostate cancer risk [pooled OR = 1.10 (1.01-1.19) per 100 pmol/L increase in B(12); P = 0.002]; the pooled OR for the association of folate with prostate cancer was positive [OR = 1.11 (0.96-1.28) per 10 nmol/L; P = 0.2) and conventionally statistically significant if ProtecT (the only case-control study) was excluded [OR = 1.18 (1.00-1.40) per 10 nmol/L; P = 0.02].


CONCLUSIONS
Vitamin B(12) and (in cohort studies) folate were associated with increased prostate cancer risk.


CONCLUSIONS
Given current controversies over mandatory fortification, further research is needed to determine whether these are causal associations.
Collin
Simon M
SM
Department of Social Medicine, University of Bristol, Bristol, United Kingdom. simon.collin@bristol.ac.uk
Metcalfe
Chris
C
Refsum
Helga
H
Lewis
Sarah J
SJ
Zuccolo
Luisa
L
Smith
George Davey
GD
Chen
Lina
L
Harris
Ross
R
Davis
Michael
M
Marsden
Gemma
G
Johnston
Carole
C
Lane
J Athene
JA
Ebbing
Marta
M
Bønaa
Kaare Harald
KH
Nygård
Ottar
O
Ueland
Per Magne
PM
Grau
Maria V
MV
Baron
John A
JA
Donovan
Jenny L
JL
Neal
David E
DE
Hamdy
Freddie C
FC
Smith
A David
AD
Martin
Richard M
RM
D000368:Aged; D016022:Case-Control Studies; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood*; D012307:Risk Factors; D014155:Transcobalamins / Q000378:metabolism*; D014805:Vitamin B 12 / Q000097:blood*
D014155:Transcobalamins; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12