Beneficial role for folate in the prevention of colorectal and breast cancer

Folate is involved in the synthesis of nucleotides and amino acid metabolism such as methylation of homocysteine to methionine. Methionine is activated by adenosine triphosphate (ATP) to produce S-adenosylme-thionine (SAM), the primary intracellular methyl donor. Thus, folate is essential for the synthesis, methylation, and repair of DNA. With regard to its biochemical function it has been hypothesized that a diminished folate status may contribute to carcinogenesis by alteration of gene expression and increased DNA damage. Animal and human studies support this hypothesis, particularly with respect to colorectal cancer. Epidemiological evidence for the association between folate status and cancer was first observed among ulcerative colitis patients. Several case-control studies demonstrated reduction in colorectal cancer risk with better folate status. Two large, prospective cohort studies support the concept that high folate intake is protective against colon cancer. In contrast to colorectal cancer, the potential association of folate status and risk has been less investigated in breast cancer. Recently, convincing epidemiological data establishing a positive effect of folate status on breast cancer risk were published. This review summarizes the epidemiological evidence for the association between folate status and colorectal and breast cancer risk. In addition, a short overview is given on the discussed mechanism(s) by which folate might be involved in carcinogenesis.