Tissue Molecular Profiles in WTC-exposed Community

New York University School Of Medicine, New York NY

Investigators

Abstract

The collapse 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. Historically, most of the research focused on first-responders. However, the impact of the WTC exposures on general population, particularly on the health of younger people and women remains poorly understood. The current application will focus on WTC-exposed non- responder women who were diagnosed with breast cancer. The epigenome acts as an interface between the genome and the environment. It is plastic, changing with environmental exposures, thereby regulating transcription. We have previously demonstrated substantial methylation differences in peripheral blood between WTC-exposed and unexposed cancer-free women. However, it is unknown whether blood-based differences correspond to changes at the breast tissue level. The overall objective of this project is to improve understanding of how WTC exposure contributed towards breast cancer development at the molecular level. The project addresses the hypothesis that WTC-exposed women with breast cancer may have tissue- specific epigenetic and transcriptomic profiles that are different from those in unexposed breast cancer patients. To test the study hypothesis, we will compare breast tissue samples of WTC-exposed and unexposed women diagnosed with breast cancer using advanced Illumina Infinium MethylationEpic arrays for global methylation analyses and Nanostring GeoMx Digital Spatial Profiler for whole transcriptome analyses. The project addresses the knowledge gap regarding breast tissue-specific epigenetic and transcriptomic changes in understudied population of WTC-exposed women survivors. Our results could lead to identification of consistent functional pathways and novel tissue-specific biomarkers that will enhance breast cancer diagnosis and treatment in this understudied population.