Associations between Intake of Folate, Methionine, and Vitamins B-12, B-6 and Prostate Cancer Risk in American Veterans

Abstract

Prostate cancer (PC) is the second leading cause of cancer death in men. Recent reports suggest that excess of nutrients involved in the one-carbon metabolism pathway increases PC risk; however, empirical data are lacking. Veteran American men (272 controls and 144 PC cases) who attended the Durham Veteran American Medical Center between 2004–2009 were enrolled into a case-control study. Intake of folate, vitamin B12, B6, and methionine were measured using a food frequency questionnaire. Regression models were used to evaluate the association among one-carbon cycle nutrients, MTHFR genetic variants, and prostate cancer. Higher dietary methionine intake was associated with PC risk (OR = 2.1; 95%CI 1.1–3.9) The risk was most pronounced in men with Gleason sum <7 (OR = 2.75; 95%CI 1.32– 5.73). The association of higher methionine intake and PC risk was only apparent in men who carried at least one MTHFR A1298C allele (OR = 6.7; 95%CI = 1.6–27.8), compared to MTHFR A1298A noncarrier men (OR = 0.9; 95%CI = 0.24–3.92) (p-interaction = 0.045). There was no evidence for associations between B vitamins (folate, B12, and B6) and PC risk. Our results suggest that carrying the MTHFR A1298C variants modifies the association between high methionine intake and PC risk. Larger studies are required to validate these findings.

Alternative Fuels for Cancer Cells

“…Given the potential involvement of HeK4me3 and H3K4 demethylase JARID1B upregulation in prostate cancer 40 , methionine restriction may affect the epigenetic landscape and oncogenesis of tumors cell driven by these epigenetic features. Given the association of methionine-related metabolites and putative therapeutic potential of methionine restriction for tumors 41,42 . While these studies focus on mouse and human stem cells, similar regulatory mechanisms are likely to be relevant in cancer cells.…”

Impact of Folate Intake on Prostate Cancer Recurrence Following Definitive Therapy: Data from CaPSURE™

“…14 Dietary deficiency or excess of nutrients involved in the 1-carbon metabolism pathway was hypothesized to increase the prostate cancer risk but evidence is inconsistent. 15–23 Numerous cancers, including prostate cancer, show a general pattern of global DNA hypomethylation and gene specific hypermethylation, 24 suggesting that 1-carbon cycle deficiency or excess may have a role in tumor development or progression. It was hypothesized that folate supplementation before pre-neoplastic lesions develop may prevent tumor by enhancing genomic DNA stability while folate supplementation may increase established cancer growth.…”

Complementary and alternative medicine: Herbals and supplements: A review for the primary care physician

“…More important, some antioxidants in high doses may even increase mortality in certain cancers; e.g., beta carotene may enhance the progression of lung cancer, especially in smokers [113][114]. The B vitamins, such as B12, B6, and folic acid, have not demonstrated a decline in risk of prostate cancer, transient ischemic attacks, or stroke, in spite of a decline in homocysteine levels [115][116][117].…”