Folate is involved in the synthesis of nucleotides and amino acid metabolis
m such as methylation of homocysteine to methionine. Methionine is activate
d by adenosine triphosphate (ATP) to produce S-adenosylme-thionine (SAM), t
he primary intracellular methyl donor. Thus, folate is essential for the sy
nthesis, methylation, and repair of DNA. With regard to its biochemical fun
ction it has been hypothesized that a diminished folate status may contribu
te to carcinogenesis by alteration of gene expression and increased DNA dam
age. Animal and human studies support this hypothesis, particularly with re
spect to colorectal cancer. Epidemiological evidence for the association be
tween 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 studi
es support the concept that high folate intake is protective against colon
cancer. In contrast to colorectal cancer, the potential association of fola
te status and risk has been less investigated in breast cancer. Recently, c
onvincing epidemiological data establishing a positive effect of folate sta
tus on breast cancer risk were published.
This review summarizes the epidemiological evidence for the association bet
ween folate status and colorectal and breast cancer risk. In addition, a sh
ort overview is given on the discussed mechanism(s) by which folate might b
e involved in carcinogenesis.