title: Body mass and DNA promoter methylation in breast tumors in the Western New York Exposures and Breast Cancer Study.
abstract: BACKGROUND
  The mechanism of the observed association between body mass, particularly centralized body fat, and postmenopausal breast cancer risk is not well understood.
  
  
  OBJECTIVE
  We hypothesized that body mass may affect DNA methylation through increased estrogen and chronic inflammation. The association between body mass and promoter methylation in breast tumors was investigated in a population-based, case-control study.
  
  
  METHODS
  The promoter methylation of E-cadherin, p16, and RAR-β(2) genes was assessed in breast tumor blocks from 803 pre- and postmenopausal cases by using real-time methylation-specific polymerase chain reaction. Unconditional logistic regression was used to derive the adjusted OR and 95% CI for case-case comparisons of tumors with and without promoter methylation of the genes.
  
  
  RESULTS
  The frequency of promoter methylation was 20% for E-cadherin, 25.9% for p16, and 27.5% for RAR-β(2). There was no difference in the prevalence of the DNA methylation of individual genes by BMI, waist-to-hip ratio (WHR), or lifetime weight change between the age of 20 y and the present. However, in a case-case comparison of postmenopausal breast cancer, a greater WHR was associated with an increased likelihood of ≥1 of the 3 genes being methylated (OR: 1.85; 95% CI: 1.10, 3.11; P-trend < 0.02).
  
  
  CONCLUSIONS
  We showed that WHR was associated with DNA promoter methylation of ≥1 of 3 genes in postmenopausal breast tumors. It may be that the association of body fat composition and postmenopausal breast cancer is related to altered DNA methylation. However, future studies in other populations and with an examination of the methylation of more genes are needed.
authors.affiliation: Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, NY, USA. menghua.tao@mssm.edu
authors.forename: Meng-Hua
authors.initials: MH
authors.lastname: Tao
authors.forename: Catalin
authors.initials: C
authors.lastname: Marian
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.forename: Christine
authors.initials: C
authors.lastname: Ambrosone
authors.forename: Shiva S
authors.initials: SS
authors.lastname: Krishnan
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Edge
authors.forename: Maurizio
authors.initials: M
authors.lastname: Trevisan
authors.forename: Peter G
authors.initials: PG
authors.lastname: Shields
authors.forename: Jo L
authors.initials: JL
authors.lastname: Freudenheim
mesh_terms: D050153:Abdominal Fat; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001835:Body Weight; D001943:Breast Neoplasms / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D016001:Confidence Intervals; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009518:New York; D056128:Obesity, Abdominal / Q000235:genetics*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D017698:Postmenopause; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000235:genetics; D049629:Waist-Hip Ratio
chemical_list: D015820:Cadherins; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta