title: Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer.
abstract: BACKGROUND
  Vitamin B(12), holo-haptocorrin, and the folate-pathway single-nucleotide polymorphisms MTR 2756A>G and SHMT1 1420C>T have been associated with an increased risk of prostate cancer. We investigated whether these and other elements of folate metabolism were associated with prostate-specific antigen (PSA) velocity (PSAV) as a proxy measure of prostate cancer progression in men with localized prostate cancer.
  
  
  METHODS
  We measured plasma folate, B(12), holo-haptocorrin, holo-transcobalamin, total transcobalamin, and total homocysteine at diagnosis in 424 men (ages 45-70 years) with localized prostate cancer in a U.K.-wide population-based cohort. Thirteen folate-pathway single-nucleotide polymorphisms were genotyped for 311 of these men. Postdiagnosis PSAV (continuous measure and with a threshold set a priori at 2 ng/mL/y) was estimated from repeat PSA measurements.
  
  
  RESULTS
  Median follow-up time was 2.5 (range, 0.8-5.6) years. Vitamin B(12), holo-haptocorrin, holo-transcobalamin, total transcobalamin, and total homocysteine were not associated with postdiagnosis PSAV. Folate was associated with an increased risk of PSAV >2 ng/mL/y [odds ratio (OR) per unit increase in log(e) concentration, 1.57; 95% confidence interval (95% CI), 0.98-2.51; P = 0.06]. MTRR 66A>G (rs1801394) was associated with a reduced risk (recessive model OR, 0.33; 95% CI, 0.11-0.97; P = 0.04), and SHMT1 1420C>T (rs1979277) with an increased risk (per-allele OR, 1.49; 95% CI, 0.93-2.37; P = 0.09) of PSAV >2 ng/mL/y.
  
  
  CONCLUSIONS
  We found weak evidence that higher folate levels may be associated with faster progression of localized prostate cancer.
  
  
  CONCLUSIONS
  Long-term follow-up is needed to test associations with metastases and mortality, and the observed genetic effects require replication.
authors.affiliation: School of Social and Community 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: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Angela
authors.initials: A
authors.lastname: Cox
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: 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; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D018450:Disease Progression; D005492:Folic Acid / Q000097:blood* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006710:Homocysteine / Q000097:blood / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D014805:Vitamin B 12 / Q000097:blood / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D006710:Homocysteine; D005492:Folic Acid; D017430:Prostate-Specific Antigen; D014805:Vitamin B 12