Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer.
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.
Collin
Simon M
SM
School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom. simon.collin@bristol.ac.uk
Metcalfe
Chris
C
Refsum
Helga
H
Lewis
Sarah J
SJ
Smith
George Davey
GD
Cox
Angela
A
Davis
Michael
M
Marsden
Gemma
G
Johnston
Carole
C
Lane
J Athene
JA
Donovan
Jenny L
JL
Neal
David E
DE
Hamdy
Freddie C
FC
Smith
A David
AD
Martin
Richard M
RM
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
D014408:Biomarkers, Tumor; D006710:Homocysteine; D005492:Folic Acid; D017430:Prostate-Specific Antigen; D014805:Vitamin B 12