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The University of Southampton
Biological Sciences

Research project: Effect of folic acid supplementation during the life course on cancer susceptibility

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Does the level and timing of folic acid supplementation during the lifecourse affect the epigenetic regulation of cancer determining genes leading to long term changes in genome stability and tissue differentiation.

The relationship between folic acid and cancer is uncertain as although most studies have shown that in adults moderate folic acid intake reduces breast cancer risk, there is also evidence that folic acid at high levels can increase susceptibility to cancer. However, to date few studies have explored the relationship between early life exposure to folic acid and later risk of breast cancer, despite evidence that environmental exposures in early life are important determinants of future disease risk. Preliminary work in our laboratory has shown that folic acid intake during specific periods in development results in altered DNA methylation and long term changes in the expression of BRCA1 and Oct4, genes involved in breast cancer risk. These findings suggest that susceptibility to cancer in adults may originate at least partly from epigenetic changes induced decades before the appearance of clinical disease by variations in micronutrient intake during key developmental periods.

This proposal addresses the general hypothesis that folic acid intake during specific periods of the life-course leads to persistent dose and tissue-dependent epigenetic changes in genes involved in determining cancer risk. 1. To determine whether the timing and level of folic acid supplementation during the life course induces long-term changes in the expression of BRCA 1 and Oct-4. 2. To determine whether persistent alterations in gene expression induced by folic acid supplementation involve changes in DNA methylation. 3. To determine whether the altered expression of BRCA1 and Oct-4 induced by folic acid supplementation leads to alterations in DNA repair, cell differentiation and tissue morphology.

Funding: WCRF March 2013-February 2016

Related research groups

Molecular and Cellular Biosciences
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