Folate and one-carbon metabolism and its impact on aberrant DNA methylation in cancer

Folate is a methyl donor that plays an essential role in DNA synthesis and biological methylation reactions, including DNA methylation. Folate deficiency may be implicated in the development of genomic DNA hypomethylation, which is an early epigenetic event found in many cancers, particularly colorectal cancer (CRC). Numerous studies employing in vitro systems, animal models, and human interventional studies have tested this hypothesis. Here, we describe the role of folate as a methyl donor in the one-carbon metabolism cycle, and the consequences of cellular folate deficiency. The existing evidence on folate and its relationship to DNA methylation is discussed using CRC as an example. While there remain numerous technical challenges in this important field of research, changes to folate intake appear to be capable of modulating DNA methylation levels in the human colonic mucosa and this may potentially alter CRC risk.