Maternal Folic Acid Supplementation and Risk of Medulloblastoma in Offspring

Abstract

Folate deficiency is reportedly the most common vitamin deficiency in the United States. Various clinical studies have researched the implications of such a deficiency on the health of individuals, particularly regarding developing embryos in expectant mothers. Such previous research has found a convincing correlation with a number of developmental abnormalities, including neural tube defects as well as a form of brain cancer known as medulloblastoma. Medulloblastoma is classified as a primitive neuralectodermal tumor (PNET) that affects the cerebellum, and it is the leading type of brain cancer occurring in children. Despite the existing theories and clinical studies that have pointed to an association between folate deficiency and medulloblastoma, it has yet to be shown that folate in fact plays a causal role in the formation of these tumors. To test our hypothesis that folate deficiency directly causes an increased incidence of medulloblastoma, we created an experiment in which three cohorts of mice of the heterozygous Ptch+/- background were fed different diets that included high, control, and low folate supplementation. After allowing these mice to breed, the offspring were observed for the development of medulloblastoma. Unexpectedly, we found a significantly lower incidence of medulloblastoma in the low folate cohort, while the differences in the high and control cohorts were not statistically significant. Our findings indicate that folate does appear to play a role in medulloblastoma formation, although whether folate actually induces the tumors or progresses preexisting ones remains unclear. Thus, future directions aiming to clarify the role of folate in cancer cells are necessary in order to fully understand the effect of folate deficiency on medulloblastoma tumorigenesis.