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Introduction 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 methylated HIN1 in breast tumor tissue. Cases with BMI≥30kg/m2 were more likely to have ER+PR+ breast tumors in the presence of unmethylated ESR1 (OR=2.63, 95% CI 1.32-5.25) and women with high RPA were more likely to have ER+PR+ breast tumors with methylated GSTP1 (OR=2.33, 95% CI 0.79-6.84). Discussion While biologically plausible, our findings that BMI is associated with methylated HIN1 and BMI/RPA are associated with ER+PR+ breast tumors in the presence of unmethylated ESR1 and methylated GSTP1, 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.

The results of this large investigation are consistent with those of most previous studies, and do not support the hypothesis that electric blanket use is associated with increased breast cancer risk.

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Background. Previous epidemiologic studies, including our own, 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. This study considers the impact on breast cancer incidence from multiple PAH exposure sources in a single model, which better reflects exposure to these complex mixtures. Methods. In a population-based case-control study conducted on Long Island, New York (N=1,508 breast cancer cases/1,556 controls), a Bayesian hierarchical regression approach was used to estimate adjusted posterior means and credible intervals (CrI) for the adjusted odds ratios (ORs) 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. Results. Most women were exposed to PAHs from multiple sources. In a hierarchical model, breast cancer incidence was positively associated with ETS from a spouse (OR=1.20, 95%CrI=1.03, 1.42) and residential synthetic firelog burning (OR=1.30, 95%CrI=1.06, 1.60). Additionally, PAH exposure groups, including ingestion (OR=1.45, 95%CrI=1.16, 1.79), indoor stove/fireplace use (OR=1.30, 95%CrI=1.02, 1.62), and total indoor sources (active smoking, ETS from spouse, grilled/smoked meat intake, stove/fireplace use, OR=1.46, 95%CrI=1.03, 2.05), were associated with increased breast cancer incidence. 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. Citation Format: White AJ, Bradshaw PT, Herring AH, Teitelbaum SL, Beyea J, Stellman SD, Steck SE, Mordukhovich I, Eng SM, Engel LS, Conway K, Hatch M, Neugut AI, Santella RM, Gammon MD. Exposure to multiple sources of polycyclic aromatic hydrocarbon and breast cancer incidence. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-09-08.