Abstract
Abstract Transient nutritional exposures during critical ontogenic periods can cause persistent changes in gene expression, metabolism, and risk of various diseases including cancer. We have been investigating whether such ‘developmental programming’ occurs via nutritional influences on developmental epigenetics. Our studies in agouti viable yellow and axin fused mice showed that developmental establishment of DNA methylation at ‘metastable epialleles’ is especially sensitive to maternal nutritional status around the time of conception. Lately, using a multiple-tissue screen for interindividual variation in DNA methylation, we have identified human genomic regions that appear to be metastable epialleles. Stochastic establishment of DNA methylation at these loci is affected by maternal nutrition around the time of conception, consistent across multiple tissues, and stable for many years. Most recently, our studies using genome-wide bisulfite sequencing have identified candidate metastable epialleles that are associated with genes implicated in human cancer, potentially providing opportunities for cancer risk assessment and prevention. Citation Format: Robert A. Waterland. Nutrition, epigenetics, and cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PL02-01.
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