title: Polycyclic aromatic hydrocarbon (PAH)-DNA adducts and breast cancer: modification by gene promoter methylation in a population-based study.
abstract: OBJECTIVE
  Polycyclic aromatic hydrocarbon (PAH)-DNA adducts have been associated with breast cancer incidence. Aberrant changes in DNA methylation may be an early event in carcinogenesis. However, possible relations between PAH-DNA adducts, methylation, and breast cancer are unknown. The objectives of this study were to (1) assess associations between PAH-DNA adducts, and breast cancer, stratified by DNA methylation markers and (2) examine interactions between adducts and DNA methylation in association with breast cancer and tumor subtype.
  
  
  METHODS
  In a population-based case-control study, promoter methylation of 13 breast cancer-related genes was measured in tumor tissue (n = 765-851 cases). Blood DNA from breast cancer cases (n = 873) and controls (n = 941) was used to assess PAH-DNA adducts and global methylation. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI); and the ratio of the OR (ROR) was used to assess heterogeneity.
  
  
  RESULTS
  Women with detectable PAH-DNA adducts and methylated RARβ (ROR 2.69, 95% CI 1.02-7.12; p for interaction = 0.03) or APC (ROR 1.76, 95% CI 0.87-3.58; p for interaction = 0.09) genes were more likely to have hormone receptor-positive tumors than other subtypes. Interactions with other methylation markers were not apparent (p ≥ 0.10). The association between adducts and breast cancer did not vary by methylation status of the tumor nor did adducts associate with global methylation in the controls.
  
  
  CONCLUSIONS
  Gene-specific methylation of RARβ, and perhaps APC, may interact with PAH-DNA adducts to increase risk of hormone receptor-positive breast cancer. There was little evidence that adducts were associated with or interacted with other methylation markers of interest.
authors.affiliation: Department of Epidemiology, University of North Carolina, CB#7435, McGavran-Greenberg Hall, Chapel Hill, NC, 27599-7435, USA. whitea@unc.edu.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: White
authors.affiliation: Departments of Preventive Medicine, Ichan School of Medicine at Mt. Sinai, New York, NY, USA.|Departments of Oncological Science, Ichan School of Medicine at Mt. Sinai, New York, NY, USA.|Departments of Pediatrics, Ichan School of Medicine at Mt. Sinai, New York, NY, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, University of North Carolina, CB#7435, McGavran-Greenberg Hall, Chapel Hill, NC, 27599-7435, USA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: McCullough
authors.affiliation: Research Center for Translational Medicine, Shanghai East Hospital of Tongji University School of Medicine, Shanghai, China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Environmental Health Sciences, Columbia University, New York, NY, USA.
authors.forename: Yoon Hee
authors.initials: YH
authors.lastname: Cho
authors.affiliation: Departments of Preventive Medicine, Ichan School of Medicine at Mt. Sinai, New York, NY, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbaum
authors.affiliation: Department of Epidemiology, Columbia University, New York, NY, USA.|Department of Medicine, Columbia University, New York, NY, USA.
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.affiliation: Department of Epidemiology, Columbia University, New York, NY, USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.affiliation: Department of Pathology, Columbia University, New York, NY, USA.
authors.forename: Hanina
authors.initials: H
authors.lastname: Hibshoosh
authors.affiliation: Department of Environmental Health Sciences, Columbia University, New York, NY, USA.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.affiliation: Department of Epidemiology, University of North Carolina, CB#7435, McGavran-Greenberg Hall, Chapel Hill, NC, 27599-7435, USA.
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D018736:DNA Adducts / Q000009:adverse effects*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D016017:Odds Ratio; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects*; D011401:Promoter Regions, Genetic; D012307:Risk Factors
chemical_list: D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; C095911:polycyclic aromatic hydrocarbons-DNA adduct
keywords: Breast cancer; DNA methylation; Polycyclic aromatic hydrocarbons