FOLATE AND COLONIC CARCINOGENESIS - SEARCHING FOR A MECHANISTIC UNDERSTANDING

A growing body of epidemiologic data indicates a relationship between folate status and the risk of developing colorectal neoplasia. Diminished folate status is associated with a higher risk of neoplasia. Interestingly, this phenomenon has been observed with relatively modest alterations in folate status and may even be present when vitamin status is diminished within the range of what is conventionally accepted as normal. A controlled laboratory study in an animal model of colorectal carcinogenesis confirmed a cause and effect relationship between folate deficiency and enhanced carcinogenesis. Possible means by which this effect may occur are discussed. Preliminary studies in humans with adenomatous polyps or colorectal cancers suggest that an intermediary marker of colonic tumorigenesis may be reversed by administering pharmacologic doses of folic acid, indicating a possible chemopreventive role for this vitamin.