title: Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis.
abstract: 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.
authors.affiliation: Department of Social Medicine, University of Bristol, Bristol, United Kingdom. simon.collin@bristol.ac.uk
authors.forename: Simon M
authors.initials: SM
authors.lastname: Collin
authors.forename: Chris
authors.initials: C
authors.lastname: Metcalfe
authors.forename: Helga
authors.initials: H
authors.lastname: Refsum
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Lewis
authors.forename: Luisa
authors.initials: L
authors.lastname: Zuccolo
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
authors.forename: Ross
authors.initials: R
authors.lastname: Harris
authors.forename: Michael
authors.initials: M
authors.lastname: Davis
authors.forename: Gemma
authors.initials: G
authors.lastname: Marsden
authors.forename: Carole
authors.initials: C
authors.lastname: Johnston
authors.forename: J Athene
authors.initials: JA
authors.lastname: Lane
authors.forename: Marta
authors.initials: M
authors.lastname: Ebbing
authors.forename: Kaare Harald
authors.initials: KH
authors.lastname: Bønaa
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.forename: Maria V
authors.initials: MV
authors.lastname: Grau
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Donovan
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.forename: A David
authors.initials: AD
authors.lastname: Smith
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
mesh_terms: 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*
chemical_list: D014155:Transcobalamins; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12