One-Carbon Metabolism and Prostate Cancer Risk: Prospective Investigation of Seven Circulating B Vitamins and Metabolites

Abstract

Purpose: 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 onecarbon 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. Materials and 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. Conclusion: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. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1538 -43)

Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer—A large nested case–control study within the JANUS cohort in Norway

“…10,11 Nevertheless, an observational population-based study previously showed positive associations of prostate cancer risk with circulating choline and vitamin B2, and a nonsignificant positive association with plasma betaine concentration. 12 These observations may support the hypothesis that high methyl group bioavailability plays a role in cancer development.…”

“…12 In our study population, high serum folate concentration was associated with modestly increased prostate cancer risk. 40 In addition, here we observed that high serine was associated with increased prostate cancer risk when folate status is low, and that for sarcosine and glycine, the inverse associations were only observed in combination with high folate status.…”

Choline and betaine in health and disease

“…Secondary analyses of the Aspirin/ Folate Polyp Prevention Study demonstrated that individuals treated with folic acid had an increased risk of prostate cancer (Figueiredo et al 2009). Notably, in the Northern Sweden Health and Disease Cohort, doubling of plasma choline was associated with 46% increase of prostate cancer risk (Johansson et al 2009). These findings point to a possible role of one-carbon metabolism in growth enhancement of prostate cancer.…”

Modulation of One-Carbon Metabolism by B Vitamins: Implications for Transformation and Progression of Prostate Cancer

“…FA supplementation was associated with a 2.6 fold increase in incidence (Figueiredo et al, 2009) and stage (Lawson et al, 2007) of prostate tumors. Collin noted serum folate-related increase in PSA velocity Others related high B12 levels to prostate cancer (Hultdin et al, 2005;Johansson et al, 2009;Weinstein et al, 2006;Vlajinac et al, 1997). We reported direct stimulation of prostate cancer by administration of B12 to a B12 deficient patient (Tisman et al, 2009) and by a supplement containing a combination of B12 and mixed folates Figures 3 and 4 (Tisman & Garcia, 2011).…”