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National Institute of Environmental Health Sciences

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Publication Detail

Title: Dietary modifications, weight loss, and changes in metabolic markers affect global DNA methylation in Hispanic, African American, and Afro-Caribbean breast cancer survivors.

Authors: Delgado-Cruzata, Lissette; Zhang, Wenfei; McDonald, Jasmine A; Tsai, Wei Yann; Valdovinos, Cristina; Falci, Laura; Wang, Qiao; Crew, Katherine D; Santella, Regina M; Hershman, Dawn L; Greenlee, Heather

Published In J Nutr, (2015 Apr)

Abstract: 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 (β = 0.19, P = 0.001) and LUMA DNA methylation levels (β = 0.24, P = 0.02), respectively. Similarly, 12-mo changes in dietary measures such as vegetable (β = 0.009, P = 0.048), protein (β = 0.04, P = 0.001), and total caloric (β = 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 (β = 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.

PubMed ID: 25833781 Exiting the NIEHS site

MeSH Terms: Adult; Aged; Biomarkers/blood; Black or African American/genetics; Blood Glucose/metabolism; Breast Neoplasms/therapy*; Cross-Over Studies; DNA Methylation/genetics*; Energy Intake; Feeding Behavior*; Female; Follow-Up Studies; Genetic Markers*; Hispanic or Latino/genetics; Humans; Life Style; Long Interspersed Nucleotide Elements/genetics; Middle Aged; Motor Activity; Nutrition Assessment; Pilot Projects; Survivors*; Weight Loss*; Young Adult

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