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British Medical Bulletin 55:578-592 (1999)
© 1999 The British Council
research-article |
Folic acid deficiency and cancer: mechanisms of DNA instability
Division of Micronutrients and Lipid Metabolism, Rowett Research Institute Aberdeen, UK
Correspondence to: Dr Susan J Duthie, Division of Micronutrients and Lipid Metabolism, Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK
Abstract
Folic acid deficiency in humans has been linked with megaloblastic anaemia, neural tube defects in the neonate, and heart disease. Folate has also been implicated in the development of cancer, especially cancer of the colorectum. There appear to be two principal mechanisms through which low folate status may increase the risk of malignancy. Folate deficiency, by reducing intracellular S-adenosylmethionine (SAM), can alter cytosine methylation in DNA, leading to inappropriate activation of proto-oncogenes and induction of malignant transformation. Alternatively, folic acid is crucial for normal DNA synthesis and repair. Folate deficiency may cause an imbalance in DNA precursors, uracil misincorporation into DNA, and chromosome breakage. This chapter briefly describes the epidemiological data supporting the involvement of folic acid in the aetiology of cancer. It also assesses the evidence from cellular, animal and human studies that folic acid can modulate DNA by such mechanisms.
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