One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites.
OBJECTIVE
Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before.


METHODS
We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression.


RESULTS
Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk.


CONCLUSIONS
The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation.
Unit of Genetic Epidemiology, IARC, Lyon 69372 Cedex 08, France. JohanssonM@fellows.iarc.fr
Mattias
M
Johansson
Bethany
B
Van Guelpen
Stein Emil
SE
Vollset
Johan
J
Hultdin
Anders
A
Bergh
Tim
T
Key
Oivind
O
Midttun
Göran
G
Hallmans
Per M
PM
Ueland
Pär
P
Stattin
D000328:Adult; D001622:Betaine / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002794:Choline / Q000097:blood; D003545:Cysteine / Q000097:blood; D006801:Humans; D008297:Male; D008715:Methionine / Q000097:blood; D008764:Methylmalonic Acid / Q000097:blood; D008875:Middle Aged; D019875:One-Carbon Group Transferases / Q000378:metabolism*; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000378:metabolism*; D012042:Registries; D012256:Riboflavin / Q000097:blood; D018709:Statistics, Nonparametric; D013548:Sweden / Q000453:epidemiology; D025101:Vitamin B 6 / Q000097:blood
D001622:Betaine; D025101:Vitamin B 6; D008764:Methylmalonic Acid; D008715:Methionine; D019875:One-Carbon Group Transferases; D003545:Cysteine; D002794:Choline; D012256:Riboflavin