One-Carbon Metabolism and Colorectal Cancer: Potential Mechanisms of Chemoprevention.

For many years folic acid has been evaluated for its utility as a chemopreventive agent due to its position at the center of the one-carbon metabolic network. This network is responsible for generating precursors to nucleotide synthesis as well as the one-carbon moieties used in DNA methylation reactions, two mechanisms which are frequently disrupted during carcinogenesis. While the use of folic acid for the chemoprevention of colorectal cancer is still controversial, there is evidence that folic acid intake has significant influence on these fundamental cellular mechanisms. Folic acid has a dual role with regards to nucleotide synthesis and colorectal cancer (CRC) prevention; in a healthy colon, adequate folate status is important for nucleotide metabolism homeostasis and the maintenance of DNA integrity, however in a colon harboring premalignant lesions lowered folate status may help to eliminate transformed cells. In addition, folic acid is important for the generation of the one-carbon groups used in DNA methylation reactions, and modulation of folic acid metabolism may be useful in combating the aberrant DNA methylation during carcinogenesis. Interestingly, it has been revealed that decreased folic acid intake can dampen the inflammatory response, which has recently been a popular strategy for colorectal cancer chemoprevention. In this review we discuss the molecular mechanisms influenced by folic acid intake and how they might be relevant to cancer chemoprevention in greater detail.