Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer

Stephanie Tuminello, Yian Zhang, Lei Yang, Nedim Durmus, Matija Snuderl, Adriana Heguy, Anne Zeleniuch-Jacquotte, Yu Chen, Yongzhao Shao, Joan Reibman and Alan A. Arslan
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Stephanie Tuminello: Department of Population Health, New York University Langone Health, New York, NY 10016, USA
Yian Zhang: Department of Population Health, New York University Langone Health, New York, NY 10016, USA
Lei Yang: Foundation Medicine, Cambridge, MA 02141, USA
Nedim Durmus: Department of Medicine, New York University Langone Health, New York, NY 10016, USA
Matija Snuderl: Department of Pathology, New York University Langone Health, New York, NY 10016, USA
Adriana Heguy: Department of Pathology, New York University Langone Health, New York, NY 10016, USA
Anne Zeleniuch-Jacquotte: Department of Population Health, New York University Langone Health, New York, NY 10016, USA
Yu Chen: Department of Population Health, New York University Langone Health, New York, NY 10016, USA
Yongzhao Shao: Department of Population Health, New York University Langone Health, New York, NY 10016, USA
Joan Reibman: Department of Medicine, New York University Langone Health, New York, NY 10016, USA
Alan A. Arslan: Department of Population Health, New York University Langone Health, New York, NY 10016, USA

IJERPH, 2022, vol. 19, issue 9, 1-15

Abstract: Breast cancer represents the most common cancer diagnosis among World Trade Center (WTC)-exposed community members, residents, and cleanup workers enrolled in the WTC Environmental Health Center (WTC EHC). The primary aims of this study were (1) to compare blood DNA methylation profiles of WTC-exposed community members with breast cancer and WTC-unexposed pre-diagnostic breast cancer blood samples, and (2) to compare the DNA methylation differences among the WTC EHC breast cancer cases and WTC-exposed cancer-free controls. Gene pathway enrichment analyses were further conducted. There were significant differences in DNA methylation between WTC-exposed breast cancer cases and unexposed prediagnostic breast cancer cases. The top differentially methylated genes were Intraflagellar Transport 74 (IFT74), WD repeat-containing protein 90 (WDR90), and Oncomodulin (OCM), which are commonly upregulated in tumors. Probes associated with established tumor suppressor genes (ATM, BRCA1, PALB2, and TP53) were hypermethylated among WTC-exposed breast cancer cases compared to the unexposed group. When comparing WTC EHC breast cancer cases vs. cancer-free controls, there appeared to be global hypomethylation among WTC-exposed breast cancer cases compared to exposed controls. Functional pathway analysis revealed enrichment of several gene pathways in WTC-exposed breast cancer cases including endocytosis, proteoglycans in cancer, regulation of actin cytoskeleton, axon guidance, focal adhesion, calcium signaling, cGMP-PKG signaling, mTOR, Hippo, and oxytocin signaling. The results suggest potential epigenetic links between WTC exposure and breast cancer in local community members enrolled in the WTC EHC program.

Keywords: environmental exposure; epigenome-wide association study; exposure assessment; methylation; pathway analysis; World Trade Center; 9/11; breast cancer (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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