Circulating folate, vitamin B 12, homocysteine, vitamin B 12 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]. Conclusion: Vitamin B12 and (in cohort studies) folate were associated with increased prostate cancer risk. Impact: Given current controversies over mandatory fortification, further research is needed to determine whether these are causal associations. ©2010 AACR.