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.

IMPACT:

Long-term follow-up is needed to test associations with metastases and mortality, and the observed genetic effects require replication.

• Authors: Simon M Collin, Chris Metcalfe, Helga Refsum, Sarah J Lewis, George Davey Smith, Angela Cox, Michael Davis, Gemma Marsden, Carole Johnston, J Athene Lane, Jenny L Donovan, David E Neal, Freddie C Hamdy, A David Smith, Richard M Martin
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 19 Issue 11 Pg. 2833-8 (Nov 2010) ISSN: 1538-7755 [Electronic] United States
• PMID: 20852008 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: ©2010 AACR.

Chemical References

• Biomarkers, Tumor
• Homocysteine
• Folic Acid
• Prostate-Specific Antigen
• Vitamin B 12

Topics

• Aged
• Biomarkers, Tumor (blood, genetics)
• Disease Progression
• Folic Acid (blood, genetics)
• Genetic Predisposition to Disease
• Genotype
• Homocysteine (blood, genetics)
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (blood, genetics, pathology)
• Signal Transduction (physiology)
• Vitamin B 12 (blood, genetics)