Dietary Modifications, Weight Loss, and Changes in Metabolic Markers Affect Global DNA Methylation in Hispanic, African American, and Afro-Caribbean Breast Cancer Survivors

Background: Lower levels of global DNA methylation in tissue and blood have been associated with increased cancer risk. Conversely, cross-sectional analyses of healthier lifestyle patterns have been associated with higher levels of global DNA methylation. Objective: In this trial, we explored the associations between changes in lifestyle modifications (diet, weight loss), metabolic markers, and global epigenetic biomarkers in white blood cells. Methods: Study participants were Hispanic, African American, and Afro-Caribbean overweight and sedentary female breast cancer survivors (n=24) who participated in a larger randomized, crossover, pilot study of a 6-mo weight loss intervention and who had available blood specimens. Anthropometric measures, a food-frequency questionnaire, and peripheral blood were collected at baseline, 6 mo, and 12 mo. Plasma samples were analyzed for metabolic markers (insulin, glucose). We measured DNA methylation of long interspersed nucleotide element 1 (LINE-1) and satellite 2 by pyrosequencing and MethyLight, respectively, and global DNA methylation by the luminometric methylation assay (LUMA). Results: DNA methylation of LINE-1 was statistically significantly elevated at 6 mo [75.5% vs. 78.5% (P< 0.0001)] and 12 mo [75.5% vs. 77.7% (P< 0.0001)], compared to baseline. Over a 12-mo period, changes in percentage body fat and plasma glucose concentrations were positively associated with LINE-1 DNA methylation (beta = 0.19, P= 0.001) and LUMA DNA methylation levels (beta = 0.24, P= 0.02), respectively. Similarly, 12-mo changes in dietary measures such as vegetable (beta = 0.009, P= 0.048), protein (beta = 0.04, P= 0.001), and total caloric (beta = 0.05, P = 0.01) intake were positively associated with changes in LUMA DNA methylation, as was intake of fruit positively associated with changes in LINE-1 DNA methylation (beta = 0.004, P= 0.02). Conclusions: Our hypothesis-generating results suggest that lifestyle modifications may be associated with changes in global DNA methylation detectable at 6 and 12 mo. These biomarkers may be useful intermediate biomarkers to use in future intervention trials. This trial was registered at clinicaltrials.gov as NCT00811824.