title: Body mass index is associated with gene methylation in estrogen receptor-positive breast tumors.
abstract: BACKGROUND
  Although obesity is associated with breast cancer incidence and prognosis, the underlying mechanisms are poorly understood. Identification of obesity-associated epigenetic changes in breast tissue may advance mechanistic understanding of breast cancer initiation and progression. The goal of this study, therefore, was to investigate associations between obesity and gene methylation in breast tumors.
  
  
  METHODS
  Using the Illumina GoldenGate Cancer I Panel, we estimated the association between body mass index (BMI) and gene methylation in 345 breast tumor samples from phase I of the Carolina Breast Cancer Study, a population-based case-control study. Multivariable linear regression was used to identify sites that were differentially methylated by BMI. Stratification by tumor estrogen receptor (ER) status was also conducted.
  
  
  RESULTS
  In the majority of the 935 probes analyzed (87%), the average beta value increased with obesity (BMI ≥ 30). Obesity was significantly associated with differential methylation (FDR q < 0.05) in just two gene loci in breast tumor tissue overall and in 21 loci among ER-positive tumors. Obesity was associated with methylation of genes that function in immune response, cell growth, and DNA repair.
  
  
  CONCLUSIONS
  Obesity is associated with altered methylation overall, and with hypermethylation among ER-positive tumors in particular, suggesting that obesity may influence the methylation of genes with known relevance to cancer. Some of these differences in methylation by obese status may influence levels of gene expression within breast cells.
  
  
  CONCLUSIONS
  If our results are validated, obesity-associated methylation sites could serve as targets for prevention and treatment research. Cancer Epidemiol Biomarkers Prev; 24(3); 580-6. ©2015 AACR.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. bhair@email.unc.edu.
authors.forename: Brionna Y
authors.initials: BY
authors.lastname: Hair
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Troester
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Sharon N
authors.initials: SN
authors.lastname: Edmiston
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Eloise A
authors.initials: EA
authors.lastname: Parrish
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Whitney R
authors.initials: WR
authors.lastname: Robinson
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Olshan
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Theresa
authors.initials: T
authors.lastname: Swift-Scanlan
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Conway
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen