ASPO Abstracts
Impact of Make Better Choices 2 (MBC2) intervention on regional patterns of DNA methylation
Category: Molecular Epidemiology & Environment
Conference Year: 2019
Abstract Body:
Purpose: The study aim was to examine the impact of the MBC2 healthy diet and activity intervention on patterns of epigenome-wide DNA methylation.Methods: The MBC2 study was a 9-month randomized controlled trial conducted between 2012-2014 among adults aged 18-65 with non-optimal levels of health behaviors. The study compared three 12-week interventions: 1) Simultaneously increase exercise and fruit/vegetable intake, while decreasing sedentary leisure screen time; 2) Sequentially increase fruit/vegetable intake and decrease leisure-screen time first, then increase exercise; 3) Control: increase sleep; decrease stress. We collected blood samples at baseline, 3 and 9 months, and measured DNA methylation using the Illumina Infinium MethylationEPIC (850k) BeadChip. We examined region-based differential methylation patterns using linear regression models with the false discovery rate of 0.05. We conducted pathway analysis using gene ontology, KEGG, and IPA canonical pathway databases. Results: We found no differences between the MBC2 population (n=340) and the subsample with DNA methylation measured (n=68) on baseline characteristics or the impact of the intervention on behavior change. We identified no differentially methylated regions at baseline between the control versus intervention groups. At three versus nine months, we identified 154 and 298 differentially methylated regions, respectively, between controls compared to pooled samples from sequential and simultaneous groups (which showed comparably large, sustained diet and activity improvements). Analysis in the GO database identified two pathways related to hemophilic cell adhesion and cell-cell adhesion via the plasma membrane. In the IPA analysis, we found pathways related to carcinogenesis including PI3K/AKT, Wnt/β-catenin, sonic hedgehog, and p53 signaling. We observed overlap between three and nine months, including the GDP-L-fucose biosynthesis I, methylmalonyl metabolism, and estrogen-mediated cell cycle regulation pathways. Conclusions: These preliminary results demonstrate that intervention producing multiple diet and activity improvements impacts patterns of DNA methylation in gene regions related to cell cycle regulation and carcinogenesis with potential implications for cancer prevention.
Keywords: DNA methylation, diet, physical activity