Background: It has been hypothesized that early life exposures are important in establishing DNA methylation patterns and that these changes may be a mechanism for alteration in breast cancer risk. We previously found an association of exposure to total suspended particulates (TSP) in early life and breast cancer risk among post-menopausal women. Particulate matter and secondhand smoke (SHS) have been associated with aberrant DNA methylation. To our knowledge the relation between early life exposure to air pollution via SHS or TSP and aberrant DNA methylation has not been examined in breast cancer tissues.
Purpose: We investigated the association between breast tumor DNA methylation in the promoter regions for 11 genes and exposure to TSP at the time of birth and SHS before age 20. We hypothesized that these exposures lead to hypermethylation of tumor suppressor genes in breast cancer tumor tissue in post-menopausal cases.
Methods: A case-case study design, utilizing breast cancer cases participating in the WEB Study, a large population-based case-control study, was used to investigate our hypotheses. Five hundred and four archived tumor blocks from breast cancer cases were retrieved, DNA was extracted and methylation of 11 genes (SFN, ESR1, GSTP1, RASSF1, RARB, SYK, SCGB3A1, CDKN2A, CCND2, BRCA1, and FHIT ) was assayed with pyrosequencing. TSP exposure at birth address was estimated with ArcGIS 8.0 (ESRI, Inc., Redlands, CA), based on annual average TSP concentrations (1959-1997). Participants reported household SHS exposure before age 20. Hypermethylation was defined as mean methylation greater than 20%. Unconditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals, adjusted for age, estrogen receptor status and current smoking status.
Results: Exposure to SHS before age 20 was associated with decreased average methylation (OR: 0.83; 95% CI: 0.50, 1.41) as was TSP exposure at birth (OR: 0.56; 95% CI: 0.29, 1.11), although these associations were imprecise. Exposure to SHS before age 20 was associated with decreased FHIT methylation (OR: 0.39; 95% CI: 0.17, 0.89). The other genes assessed showed similar inverse risk estimates and imprecision.
Conclusions: While our results are necessarily preliminary, they are not consistent with our hypothesis that TSP or SHS exposure in early life is associated with DNA hypermethylation of promoter regions of genes in breast cancer tumor tissue. Inferences are complicated by several limitations. For instance, air pollution may have a stronger impact on global DNA hypomethylation. However these findings could also be attributed to low variability in exposures, relatively small sample size, or the choice of loci and genes assayed.
Citation Format: Catherine Callahan, Matthew Bonner, Peter Shields, Christine Ambrosone, Daikwon Han, Jing Nie, Stephen Edge, Maurizio Trevisan, Jo L. Freudenheim. Early life exposure to air pollution and promoter methylation in breast tumors in the Western New York Exposures and Breast Cancer Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 265. doi:10.1158/1538-7445.AM2014-265