Alexandra J White1, Jia Chen2, Susan L Teitelbaum3, Lauren E McCullough4, Xinran Xu5, Yoon Hee Cho6, Kathleen Conway4, Jan Beyea7, Steven D Stellman8, Susan E Steck9, Irina Mordukhovich4, Sybil M Eng8, Mary Beth Terry8, Lawrence S Engel4, Maureen Hatch10, Alfred I Neugut11, Hanina Hibshoosh12, Regina M Santella13, Marilie D Gammon4. 1. Department of Epidemiology University of North Carolina, Chapel Hill, NC, USA. Electronic address: whitea@unc.edu. 2. Departments of Preventive Medicine, New York, NY, USA; Departments of Oncological Science, New York, NY, USA; Departments of Pediatrics, Ichan School of Medicine at Mt. Sinai, New York, NY, USA. 3. Departments of Preventive Medicine, New York, NY, USA. 4. Department of Epidemiology University of North Carolina, Chapel Hill, NC, USA. 5. Departments of Preventive Medicine, New York, NY, USA; Departments of Biometrics, Roche Product Development in Asia-Pacific, Shanghai, China. 6. Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, USA. 7. Department of Consulting in the Public Interest (CIPI), Lambertville, NJ, USA. 8. Departments of Epidemiology, Columbia University, New York, NY, USA. 9. Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA. 10. Departments of Division of Cancer Epidemiology and Genetics, Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA. 11. Departments of Epidemiology, Columbia University, New York, NY, USA; Departments of Medicine, Columbia University, New York, NY, USA. 12. Departments of Pathology and Cell Biology, Columbia University, New York, NY, USA. 13. Departments of Environmental Health Sciences; Columbia University, New York, NY, USA.
Abstract
BACKGROUND: Tobacco smoke, diet and indoor/outdoor air pollution, all major sources of polycyclic aromatic hydrocarbons (PAHs), have been associated with breast cancer. Aberrant methylation may be an early event in carcinogenesis, but whether PAHs influence the epigenome is unclear, particularly in breast tissue where methylation may be most relevant. We aimed to evaluate the role of methylation in the association between PAHs and breast cancer. METHODS: In a population-based case-control study, we measured promoter methylation of 13 breast cancer-related genes in breast tumor tissue (n=765-851 cases) and global methylation in peripheral blood (1055 cases/1101 controls). PAH sources (current active smoking, residential environmental tobacco smoke (ETS), vehicular traffic, synthetic log burning, and grilled/smoked meat intake) were evaluated separately. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: When comparing methylated versus unmethylated genes, synthetic log use was associated with increased ORs for CDH1 (OR=2.26, 95%CI=1.06-4.79), HIN1 (OR=2.14, 95%CI=1.34-3.42) and RARβ (OR=1.80, 95%CI=1.16-2.78) and decreased ORs for BRCA1 (OR=0.44, 95%CI=0.30-0.66). Residential ETS was associated with decreased ORs for ESR1 (OR=0.74, 95%CI=0.56-0.99) and CCND2 methylation (OR=0.65, 95%CI=0.44-0.96). Current smoking and vehicular traffic were associated with decreased ORs for DAPK (OR=0.53, 95%CI=0.28-0.99) and increased ORs for TWIST1 methylation (OR=2.79, 95%CI=1.24-6.30), respectively. In controls, synthetic log use was inversely associated with LINE-1 (OR=0.59, 95%CI=0.41-0.86). DISCUSSION: PAH sources were associated with hypo- and hypermethylation at multiple promoter regions in breast tumors and LINE-1 hypomethylation in blood of controls. Methylation may be a potential biologic mechanism for the associations between PAHs and breast cancer incidence. Published by Elsevier Inc.
BACKGROUND:Tobacco smoke, diet and indoor/outdoor air pollution, all major sources of polycyclic aromatic hydrocarbons (PAHs), have been associated with breast cancer. Aberrant methylation may be an early event in carcinogenesis, but whether PAHs influence the epigenome is unclear, particularly in breast tissue where methylation may be most relevant. We aimed to evaluate the role of methylation in the association between PAHs and breast cancer. METHODS: In a population-based case-control study, we measured promoter methylation of 13 breast cancer-related genes in breast tumor tissue (n=765-851 cases) and global methylation in peripheral blood (1055 cases/1101 controls). PAH sources (current active smoking, residential environmental tobacco smoke (ETS), vehicular traffic, synthetic log burning, and grilled/smoked meat intake) were evaluated separately. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: When comparing methylated versus unmethylated genes, synthetic log use was associated with increased ORs for CDH1 (OR=2.26, 95%CI=1.06-4.79), HIN1 (OR=2.14, 95%CI=1.34-3.42) and RARβ (OR=1.80, 95%CI=1.16-2.78) and decreased ORs for BRCA1 (OR=0.44, 95%CI=0.30-0.66). Residential ETS was associated with decreased ORs for ESR1 (OR=0.74, 95%CI=0.56-0.99) and CCND2 methylation (OR=0.65, 95%CI=0.44-0.96). Current smoking and vehicular traffic were associated with decreased ORs for DAPK (OR=0.53, 95%CI=0.28-0.99) and increased ORs for TWIST1 methylation (OR=2.79, 95%CI=1.24-6.30), respectively. In controls, synthetic log use was inversely associated with LINE-1 (OR=0.59, 95%CI=0.41-0.86). DISCUSSION: PAH sources were associated with hypo- and hypermethylation at multiple promoter regions in breast tumors and LINE-1 hypomethylation in blood of controls. Methylation may be a potential biologic mechanism for the associations between PAHs and breast cancer incidence. Published by Elsevier Inc.
Entities:
Keywords:
Air pollution; Environmental tobacco smoke; Grilled meat.; Methylation; Smoking
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