A new study recently presented at the annual American Association for Cancer Research (AACR) Meeting in Washington, D.C. has reported that offspring of rats fed a diet supplemented with folic acid during pregnancy and for a short period after birth were more likely to develop mammary tumors. The authors investigated the associations between folic acid supplementation, global DNA methylation, DNA methyltransferase (DNMT) activity, and mammary tumors in the rat offspring. Widespread loss of genomic DNA methylation is a step that occurs consistently early in breast cancer development. Folate has been shown to influence both genomic DNA methylation and cancer risk.

For three weeks prior to breeding, throughout pregnancy and nursing, and for a short period after weaning, female Sprague-Dawley rats were administered either a control diet (2 mg folic acid/kg) or a diet supplemented with folic acid (5 mg). At this point, the experimental focus turned to their offspring. Upon weaning, female pups were assigned randomly to either the control or supplemented diet. At seven weeks, all of the offspring received a single dose a carcinogen known to induce mammary tumors. At 28 weeks of age, folate levels in plasma, mammary gland and liver were measured and plasma homocysteine concentrations were determined. At the same time, mammary tumors were counted.

Genomic DNA methylation was decreased by maternal folic acid supplementation among tumor-free offspring. In pups bearing at least one mammary tumor, genomic DNA methylation was reduced significantly regardless of dietary folic acid level. Postweaning folic acid supplementation also was found to independently reduce DNMT activity in the offspring. The authors conclude that decreased genomic DNA methylation and DNMT activity associated with maternal and postweaning folic acid supplementation might be a mechanism by which maternal and postweaning folic acid supplementation increased mammary tumorigenesis in the offspring. The authors further comment that, given the drastic increase in folic acid intake among women of childbearing age in North America, future studies are need to determine whether folic acid supplementation increases the risk of breast cancer.