Vitamin Bs, One Carbon Metabolism and Prostate Cancer

K.      V. Donkena; H.      Yuan; C.      Y.F. Young

Abstract

Somatic genetic and epigenetic alterations have been suggested to be crucially involved in development and progression of cancers including prostate cancer (PCa). Epigenetic alterations such as chemical modification of chromatin associated proteins and DNA methylation can largely affect gene expression that may be important for early normal organ development, and also produces favorable conditions for cancer cell formation, growth, and survival. Aberrant DNA methylation (hyper- or hypo-methylation) may lead to chromosomal instability, and transcriptional gene silencing for tumor suppressors or overexpression for oncogenes. Vitamin Bs play important roles in one carbon metabolism that provides critical metabolites for DNA methylation, DNA repair and nucleic acid synthesis. Nutrition uptake and circulating levels of these vitamin Bs as well as genetic polymorphisms of related key enzymes in the one carbon metabolism pathway may govern bioavailability of the metabolites, and therefore to affect the phenotypic changes (e.g., cellular malignancy) via genetic and epigenetic alterations. This article will summarize recent new findings from laboratory, epidemiological or clinical trial studies regarding influence of vitamin B and one carbon metabolism on PCa development or progression.

Keywords: One carbon metabolism, folate, folic acid, DNA methylation, vitamin B6, vitamin B12, SNP, prostate cancer, Vitamin Bs, Carbon Metabolism, Aberrant DNA methylation, cellular malignancy, vitamin B, lung cancer, Androgen ablation, micronutrients, vitamin B2, dihyrofolate reductase, tetrahydrofolic acid, formyl folylpolyglutamates, 5-methyltetrahydrofolic acid, 5-methyl THF, deoxythymidylate, thymidylate synthase, antifolate agents, methotrexate, fluorouracil, hyper-methylation, adenosylhomocysteine, Methyl-Donor Nutrients, hypomethylation, O6-methylguanine-DNA methyltransferase, 8-oxoguanine-DNA glycosylase, 8-oxo-7,8-dihydroguanine, choline and methionine deficient, insulin-like growth factor 2, dimethyl-H3K9, beta-catenin, Alpha-Tocopherol, methylmalonic acid