Plasma folate, vitamin B12, and homocysteine and prostate cancer risk: A prospective study

Abstract

The role of folate metabolism in cancer development is a topic of much current interest, with maintenance of adequate folate status tending to show a protective effect. Aberrant methylation, primarily hypermethylation of certain genes including tumor suppressors, has been implicated in prostate cancer development. Folate, vitamin B12 and homocysteine are essential for methyl group metabolism and thus also for DNA methylation. We related plasma levels of these factors to prostate cancer risk in a prospective study of 254 case subjects and 514 matched control subjects. Increasing plasma levels of folate and vitamin B12 were statistically significantly associated with increased prostate cancer risk, with an odds ratio of 1.60 (95% CI = 1.03-2.49; p(trend) = 0.02) for folate and 2.63 (95% CI = 1.61-4.29; p(trend) < 0.001) for vitamin B12 for highest vs. lowest quartile. Increasing plasma homocysteine levels were associated with a reduced risk of borderline significance (OR = 0.67; 95% CI = 0.43-1.04; p(trend) = 0.08). After adjustment for the other 2 plasma variables, body mass index and smoking, a statistically significant increased risk remained only for vitamin B12 (OR = 2.96; 95% CI = 1.58-5.55; p(trend) = 0.001). Adjusted OR for folate and homocysteine were 1.30 (95% CI = 0.74-2.24; p(trend) = 0.17) and 0.91 (95% CI = 0.51-1.58; p(trend) = 0.60), respectively. Our results suggest that factors contributing to folate status are not protective against prostate cancer. On the contrary, vitamin B12, associated with an up to 3-fold increase in risk, and possibly also folate, may even stimulate prostate cancer development. These findings are novel and should be explored further in future studies.

Serum levels of folate, lycopene, β-carotene, retinol and vitamin E and prostate cancer risk

“…Prospective studies of serum folate levels have been reported to variously show a null association (Weinstein et al, 2003), and increased serum levels to either decrease (Rossi et al, 2006) or increase (Hultdin et al, 2005) the risk of subsequently developing prostate cancer. Similar ambivalent findings have been reported for b-carotene and lycopene concentrations.…”

Dietary intake and status of folate and vitamin B12 and their association with homocysteine and cardiovascular disease in European populations

“…However, studies with data on folate status but not on intake, supported the notion that folate status in the abovementioned countries was low (Nurk et al, 2004;Hultdin et al, 2005). As a result, the Hcy levels in the Netherlands and Sweden were also relatively high.…”

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

“…5 Results from observational studies suggest that high concentrations of circulating folate or high vitamin B12 status are associated with increased prostate cancer risk, although reported associations were modest and sometimes inconsistent. [6][7][8] Although increased prostate cancer risk was suggested in one trial among subjects receiving folic acid supplements, 9 recent meta-analyses did not suggest an association with increased prostate cancer risk. 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.…”