Grant: CAG/CCFC/CIHR Summer Studentship for Research in Gastroenterology

Folate and folic acid (FA), the synthetic form of this B-vitamin that is used in supplements and in fortified foods, may prevent or promote colorectal cancer depending on the timing of intervention. Intrauterine exposure to FA has drastically increased in Canada due to mandatory FA fortification and to periconceptional FA supplementation in women. DNA methylation patterns are reprogrammed during embryogenesis and hence, DNA methylation of the developing fetus may be highly susceptible to environmental modifiers including dietary factors. Folate, as a critical cofactor in one-carbon transfer reactions, plays an important role in DNA methylation and we have previously shown that maternal FA supplementation provided in utero and postnatally significantly reduces genomic DNA methylation in the colorectum in the offspring in a rat model. Aberrant patterns and dysregulation of genomic and gene-specific DNA methylation are mechanistically related to the development of colorectal cancer. We propose to investigate the effect of maternal FA supplementation on gene-specific promoter methylation of the ER, Igf2, p53, Apc and p16 genes in the colorectum of the offspring using DNA extracted from the previous animal experiment. In those genes that are associated with aberrant promoter methylation, whether this epigenetic change results in functionally significant inactivation or aberrant expression of the genes will be determined. The critical question that we wish to ask in this proposal is: Can maternal FA supplementation provided in utero and postnatally have a permanent and heritable epigenetic effect on the colon of the offspring with consequent functional ramifications, which may lead to the development of colorectal cancer in adulthood? The question of whether or not FA supplementation may adversely affect human health is a legitimate significant public health concern because it may be associated with potentially very serious consequences for many generations.