Abstract 5610: Air pollution exposure and promoter methylation of E-cadherin, p16, and RAR-β in breast cancer tumors from cases in the WEB study
Authors: Dobson Katharine A. , Freudenheim Jo L. , Shields Peter G. , Tao Meng H. , Marian Catalin , Nie Jing , Edge Stephen B. , Winston Janet S. , Trevisan Maurizio , Bonner Matthew R. 
Published: June 2012

Abstract
Purpose: Aberrant methylation has been shown to be associated with breast cancer tumor tissue samples and ambient air pollution exposure has been shown to be associated with aberrant methylation of gene promoter regions; we investigated potential associations between air pollution exposure in early life and promoter methylation of genes among breast cancer tumors.
Methods: Paraffin embedded, formalin fixed tumor tissue blocks were obtained for 803 breast cancer cases participating in the WEB study and assayed for DNA methylation status of three promoters regions of E-cadherin, p16 and RAR-β. Methylation specific PCR was used to determine methylation status. Historical annual ambient total suspended particulate matter (TSP) concentration (μg/m3) was collected from 87 air monitoring sites in Erie and Niagara Counties dating as far back as the late 1950's. Residential addresses were obtained for the time of birth, time of menarche, time of first birth if applicable, and 10 years prior to diagnosis with breast cancer. Using Arc View software, the addresses were geocoded and overlaid with the air pollution information to estimate exposure to TSP at each time point. TSP exposures varied greatly over time, therefore they were categorized into high and low based on the mean exposure among the non-breast cancer controls in the WEB study. This analysis consists of case-case comparisons, comparing TSP exposure to DNA methylation status among breast cancer patients. Odds ratios and 95% confidence limits were calculated with unconditional logistic regression, adjusting for potential confounders. We stratified all analyses by menopausal status.
Results: Among pre- but not postmenopausal women, there was an increased likelihood of a case having methylation of the p16 promoter region for those exposed to &gt;109.03 μg/m3 of TSP at first birth compared to those exposed to ≤109.03 μg/m3 (n=123; OR=6.5, 95% CI: 1.2-34. 1). E-cadherin promoter region methylation was inversely associated with high TSP at birth (&gt; 137.88 μg/m3) among the pre-menopausal women (n=138; OR=0.2, 95% CI: 0.1-0.8) but not for post-menopausal women (n=289; OR=0.8, 95% CI: 0.4-1.6) nor for the other genes. There was no evidence of association between TSP exposures and RAR-β promoter region methylation for any of the time periods.
Conclusion: Air pollution exposure at birth was much higher than exposure at later times due to increasing regulation. Exposure to higher levels of TSP at birth was associated with decreased likelihood of promoter region methylation for E-cadherin, particularly for premenopausal cases. TSP exposure at the time of a first birth was associated with increased likelihood of p16 promoter methylation in pre- but not postmenopausal breast tumors. While our results are necessarily preliminary, they suggest that exposure to air pollutants in early life may affect promoter methylation of E-cadherin and p16 genes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5610. doi:10.1158/1538-7445.AM2011-5610