title: Dietary modifications, weight loss, and changes in metabolic markers affect global DNA methylation in Hispanic, African American, and Afro-Caribbean breast cancer survivors.
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.
authors.affiliation: Departments of Environmental Health Sciences, Department of Sciences, John Jay College of Criminal Justice, City University of New York, New York, NY.
authors.forename: Lissette
authors.initials: L
authors.lastname: Delgado-Cruzata
authors.affiliation: Biostatistics, and.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Epidemiology, Mailman School of Public Health.
authors.forename: Jasmine A
authors.initials: JA
authors.lastname: McDonald
authors.affiliation: Biostatistics, and.
authors.forename: Wei Yann
authors.initials: WY
authors.lastname: Tsai
authors.affiliation: Epidemiology, Mailman School of Public Health.
authors.forename: Cristina
authors.initials: C
authors.lastname: Valdovinos
authors.affiliation: Epidemiology, Mailman School of Public Health.
authors.forename: Laura
authors.initials: L
authors.lastname: Falci
authors.affiliation: Departments of Environmental Health Sciences.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Epidemiology, Mailman School of Public Health, Herbert Irving Comprehensive Cancer Center, and Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY; and.
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Crew
authors.affiliation: Departments of Environmental Health Sciences, Herbert Irving Comprehensive Cancer Center, and.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.affiliation: Epidemiology, Mailman School of Public Health, Herbert Irving Comprehensive Cancer Center, and Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY; and.
authors.forename: Dawn L
authors.initials: DL
authors.lastname: Hershman
authors.affiliation: Epidemiology, Mailman School of Public Health, Herbert Irving Comprehensive Cancer Center, and hg2120@columbia.edu.
authors.forename: Heather
authors.initials: H
authors.lastname: Greenlee
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001943:Breast Neoplasms / Q000628:therapy*; D018592:Cross-Over Studies; D019175:DNA Methylation / Q000235:genetics*; D002149:Energy Intake; D005247:Feeding Behavior; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008019:Life Style; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008875:Middle Aged; D009043:Motor Activity; D015596:Nutrition Assessment; D010865:Pilot Projects; D017741:Survivors; D015431:Weight Loss; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D005819:Genetic Markers
keywords: LINE-1; LUMA; Sat2; epigenetics; weight loss
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