title: Gene-Specific Promoter Methylation Status in Hormone-Receptor-Positive Breast Cancer Associates with Postmenopausal Body Size and Recreational Physical Activity.
abstract: BACKGROUND
  Breast cancer, the leading cancer diagnosis among American women, is positively associated with postmenopausal obesity and little or no recreational physical activity (RPA). However, the underlying mechanisms of these associations remain unresolved. Aberrant changes in DNA methylation may represent an early event in carcinogenesis, but few studies have investigated associations between obesity/RPA and gene methylation, particularly in postmenopausal breast tumors where these lifestyle factors are most relevant.
  
  
  METHODS
  We used case-case unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the associations between body mass index (BMI=weight [kg]/height [m2]) in the year prior to diagnosis, or RPA (average hours/week), and methylation status (methylated vs. unmethylated) of 13 breast cancer-related genes in 532 postmenopausal breast tumor samples from the Long Island Breast Cancer Study Project. We also explored whether the association between BMI/RPA and estrogen/progesterone-receptor status (ER+PR+ vs. all others) was differential with respect to gene methylation status. Methylation-specific PCR and the MethyLight assay were used to assess gene methylation.
  
  
  RESULTS
  BMI 25-29.9kg/m2, and perhaps BMI≥30kg/m2, was associated with methylatedHIN1in breast tumor tissue. Cases with BMI≥30kg/m2were more likely to have ER+PR+ breast tumors in the presence of unmethylatedESR1(OR=2.63, 95% CI 1.32-5.25) and women with high RPA were more likely to have ER+PR+ breast tumors with methylatedGSTP1(OR=2.33, 95% CI 0.79-6.84).
  
  
  CONCLUSIONS
  While biologically plausible, our findings that BMI is associated with methylatedHIN1and BMI/RPA are associated with ER+PR+ breast tumors in the presence of unmethylatedESR1and methylatedGSTP1, respectively, warrant further investigation. Future studies would benefit from enrolling greater numbers of postmenopausal women and examining a larger panel of breast cancer-related genes.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill; Chapel Hill, NC, 27599, USA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: McCullough
authors.affiliation: Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai; New York, NY, 10016, USA ; Department of Pediatrics, Icahn School of Medicine at Mount Sinai; New York, NY, 10016, USA ; Department of Oncological Science, Icahn School of Medicine at Mount Sinai; New York, NY, 10016, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill; Chapel Hill, NC, 27599, USA.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: White
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, 10027, USA.
authors.forename: Yoon Hee
authors.initials: YH
authors.lastname: Cho
authors.affiliation: Department of Nutrition, University of North Carolina at Chapel Hill; Chapel Hill, NC, 27599, USA.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Bradshaw
authors.affiliation: Department of Epidemiology, Columbia University; New York, NY, 10027, USA.
authors.forename: Sybil M
authors.initials: SM
authors.lastname: Eng
authors.affiliation: Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai; New York, NY, 10016, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbaum
authors.affiliation: Department of Epidemiology, Columbia University; New York, NY, 10027, USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.affiliation: Department of Environmental Health Sciences, Columbia University; New York, NY, 10027, USA.
authors.forename: Gail
authors.initials: G
authors.lastname: Garbowski
authors.affiliation: Department of Epidemiology, Columbia University; New York, NY, 10027, USA ; Department of Medicine, Columbia University; New York, NY, 10027, USA.
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.affiliation: Department of Pathology, Columbia University; New York, NY, 10027, USA.
authors.forename: Hanina
authors.initials: H
authors.lastname: Hibshoosh
authors.affiliation: Department of Environmental Health Sciences, Columbia University; New York, NY, 10027, USA.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill; Chapel Hill, NC, 27599, USA.
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
keywords: Body mass index; breast cancer; epidemiology; gene methylation; physical activity