Steven Stellman - Sources of polycyclic aromatic hydrocarbons are associated with gene-specific promoter methylation in women with breast cancer

Document created by Steven Stellman on Dec 1, 2016
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  White, A. J., Chen, J., Teitelbaum, S. L., McCullough, L. E., Xu,   X., Hee Cho, Y., Conway, K., Beyea, J., Stellman, S. D., Steck,   S. E., Mordukhovich, I., Eng, S. M., Beth Terry, M., Engel, L.   S., Hatch, M., Neugut, A. I., Hibshoosh, H., Santella, R. M.,   Gammon, M. D. 145 93-100-

  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 RARbeta (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.

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