MULTIPLE SOURCES OF PAH EXPOSURE, DNA METHYLATION AND BREAST CANCER Public Deposited

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  • March 19, 2019
Creator
  • White, Alexandra
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Purpose. Epidemiologic studies have consistently linked long-term exposure to single-source polycyclic aromatic hydrocarbons (PAHs) to increased breast cancer incidence. It is unclear whether single sources, specific groups, or all PAH sources should be targeted for breast cancer risk reduction. Aberrant methylation may be an early event in carcinogenesis, but whether PAHs influence the epigenome is unclear. Few studies have evaluated whether PAHs are associated with methylation, particularly in breast tumors where methylation changes are particularly relevant. Methods. In a population-based case-control study (N=1,508 cases/1,556 controls), Bayesian hierarchical regression was used to estimate adjusted odds ratios (ORs and credible intervals (CrI) for PAH exposure sources, considered singly and as groups: active smoking; residential environmental tobacco smoke (ETS); indoor and outdoor air pollution; and grilled/smoked meat intake. Promoter methylation of 13 breast cancer-related genes in breast tumor tissue (n=765-851 cases) and global methylation in peripheral blood (1,055 cases/1,101 controls) were measured. Logistic regression was used to estimate ORs and 95% confidence intervals (CIs) for the association between individual PAH sources and methylation levels. Results. Breast cancer incidence was positively associated with ETS from a spouse (OR=1.20, 95%CrI=1.03, 1.40) and residential synthetic firelog burning (OR=1.29, 95%CrI=1.06, 1.57). Additionally, PAH exposure groups, including ingestion (OR=1.44, 95%CrI=1.16, 1.78) and total indoor sources (active smoking, ETS from spouse, grilled/smoked meat intake, stove/fireplace use, OR=1.45, 95%CrI=1.02, 2.04), were associated with increased breast cancer incidence. When comparing methylated versus unmethylated genes in tumor tissue, synthetic log use, residential ETS, current smoking and vehicular traffic were associated with both increased and decreased odds of methylation at a number of breast cancer-related genes. In controls, synthetic log use was inversely associated with LINE-1 methylation (OR=0.59, 95%CI=0.41-0.86). Conclusions. Groups of PAH sources, especially those for ingestion and indoor sources, were associated with a 30-50% increase in breast cancer incidence. PAH exposure is ubiquitous and a potentially modifiable breast cancer risk factor. 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.
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  • In Copyright
Advisor
  • Gammon, Marilie D.
  • Engel, Lawrence
  • Santella, Regina
  • Herring, Amy
  • Conway-Dorsey, Kathleen
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2015
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  • Chapel Hill, NC
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