The terrorist attacks and the destruction of the World Trade Center on September 11, 2001 resulted in the massive release of dust, gas, and fumes with potential exposure to known and suspected carcinogens for thousands of individuals. Most of the research to date focused on first-responders. However, the impact on the WTC disaster on the general population, particularly on women’s health remains poorly understood. The current application will focus on women as underrepresented group in previous WTC- related studies. Increasing data demonstrates that epigenetic changes may serve as objective markers of exposure to environmental chemicals. The current application will test the hypothesis that complex WTC exposures resulted in distinct long-term DNA methylation changes detectable many years after the original WTC exposure. The overarching objective of the project is to validate DNA methylation profiles of the WTC-exposed breast cancer cases observed in the pilot study using independent set of WTC-exposed and unexposed subjects. Global DNA methylation will be assessed in peripheral white blood cells DNA using Illumina Infinium MethylationEpic arrays which provide single-base methylation information for over 850,000 cytosine-phosphate-guanine sites throughout the human genome and is a comprehensive solution for epigenome-wide association studies. The project is expected to contribute to the understanding of the possible role of global DNA methylation as objective marker of potentially carcinogenic exposures among WTC survivor population, specifically women. The present proposal will address a knowledge gap on the impact of WTC disaster among women survivors. If the results confirm a correlation between WTC exposures and altered DNA methylation, it would lead to the development of novel objective biomarkers that could be used for screening and early detection of breast cancer, the most common cancer among WTC-exposed women.