Relevance of folate metabolism in the pathogenesis of colorectal cancer

The purpose of this review is to outline the principal mechanisms involved in folate metabolism and how they may relate to the pathogenesis of colorec tal cancer (CRC). In recent years, mild folate depletion (low normal level) has been associated with an increased risk of developing certain cancers, in particular colorectal neoplasia. The epidemiologic and mechanistic evide nce linking folate deficiency with carcinogenesis is reviewed, with a parti cular emphasis on colorectal neoplasia. Methylenetetrahydrofolate reductase (MTHFR) is a critical folate metabolizing enzyme, and a functional polymor phic variant of this enzyme, the so-called thermolabile variant, caused by a C677T transition in the MTHFR gene, is common in the general population. This review critically examines the evidence that suggests that carriers of this C677T variant may be at increased risk of developing colorectal neopl asia. Although folate depletion may predispose to the initiation of the neo plastic process, folate supplementation, on the other hand, might potentiat e the progression of an already established early neoplastic clone (eg, a c olorectal adenoma). This could have potential public health implications, g iven an increasingly widespread policy of folate supplementation of food st aples.