Folic acid fortification and cancer risk

Roger Bayston and colleagues1 state that, to the best of our knowledge, folic acid does not reduce colorectal cancer risk but neither does it increase it. Although the question surrounding this type of cancer is still debated, we want to underline the possibility that folic acid fortification could have many more beneficial effects than merely those on neural tube defects. Lack of maternal folate supplementation has been associated with an increased risk of childhood leukaemia, possibly resulting from DNA hypomethylation and strand breakage.2 Susceptibility to some types of cancer has been linked to the methylation level of the gene encoding cyclin-dependent kinase inhibitor 2A (CDKN2A), and there seems to be an interesting association between folate concentrations and consequent hypermethylation of such genes.3 Decreased dietary folate has also been associated with epigenetic silencing of CDKN2A in solid tumours, and this relation has been shown to be modified by the MTHFR genotype, suggesting a mechanism of action of folate deficiency in cancer.4 The folate pathways that maintain cell homoeostasis and genomic integrity during cellular division could represent an essential step in our understanding of the biology of cancers. Additional experimental and clinical observations could help clarify the role of folate concentrations and methylation of genes such as CDKN2A in the homoeostasis of normal and malignant blood cells. To avoid the risk of colon cancer, perhaps a genetic analysis of patients could be done to identify individuals with the MTHFR 677TT genotype, which could be the only condition in which high concentrations of folate might promote colon cancer development.5 We declare that we have no conflict of interest.