Other one-carbon micronutrients and age modulate the effects of folate on colorectal carcinogenesis

Abstract

Epidemiologic observations as well as preclinical studies in animal and cell culture models indicate that diminished folate status increases the risk of carcinogenesis in certain tissues.1,2 The biological plausibility of these observations is underscored by the fact that folate is an essential cofactor in biological methylation and nucleotide synthesis,3,4 and it is presently believed that anomalies in DNA methylation and in DNA synthesis are among the most common molecular alternations that contribute to the development of human neoplasia.5,6 The data in this regard is most compelling for the colorectum, but increasing evidence is accruing for similar effects in the breast and possibly in other organs. However, as we go about fully defining this effect, it is important to remain cognizant of the fact that a variety of factors interact with folate status and thereby further modulate folate's effects on carcinogenesis. The maintenance of normal patterns of biological methylation and nucleotide synthesis depends not only upon the adequate availability of folate but also on the adequate availability of other one-carbon nutrients, including vitamins B2, B6, and B12.7–9 These vitamins assume critical roles as cofactors in the one-carbon metabolic network in conjunction with folate. Thus, the metabolic functions of all these one-carbon vitamins are highly interdependent. Aberrant signaling along the Wnt pathway is an early event in 90% of human colorectal cancers and is thought …