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

Author

Listed:
  • 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
    NYU Langone’s Genome Technology Center, New York, NY 10016, USA)

  • Anne Zeleniuch-Jacquotte

    (Department of Population Health, New York University Langone Health, New York, NY 10016, USA
    NYU Perlmutter Comprehensive Cancer Center, New York, NY 10016, USA)

  • Yu Chen

    (Department of Population Health, New York University Langone Health, New York, NY 10016, USA
    NYU Perlmutter Comprehensive Cancer Center, New York, NY 10016, USA)

  • Yongzhao Shao

    (Department of Population Health, New York University Langone Health, New York, NY 10016, USA
    NYU Perlmutter Comprehensive Cancer Center, 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
    NYU Perlmutter Comprehensive Cancer Center, New York, NY 10016, USA
    Department of Obstetrics and Gynecology, New York University Langone Health, New York, NY 10016, USA)

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.

Suggested Citation

  • Stephanie Tuminello & Yian Zhang & Lei Yang & Nedim Durmus & Matija Snuderl & Adriana Heguy & Anne Zeleniuch-Jacquotte & Yu Chen & Yongzhao Shao & Joan Reibman & Alan A. Arslan, 2022. "Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer," IJERPH, MDPI, vol. 19(9), pages 1-15, April.
    • Handle: RePEc:gam:jijerp:v:19:y:2022:i:9:p:5104-:d:799618
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    References listed on IDEAS

    as
    1. Yongzhao Shao & Nedim Durmus & Yian Zhang & Sultan Pehlivan & Maria-Elena Fernandez-Beros & Lisette Umana & Rachel Corona & Adrienne Addessi & Sharon A. Abbott & Sheila Smyth-Giambanco & Alan A. Arsla, 2021. "The Development of a WTC Environmental Health Center Pan-Cancer Database," IJERPH, MDPI, vol. 18(4), pages 1-18, February.
    2. Alan A. Arslan & Stephanie Tuminello & Lei Yang & Yian Zhang & Nedim Durmus & Matija Snuderl & Adriana Heguy & Anne Zeleniuch-Jacquotte & Yongzhao Shao & Joan Reibman, 2020. "Genome-Wide DNA Methylation Profiles in Community Members Exposed to the World Trade Center Disaster," IJERPH, MDPI, vol. 17(15), pages 1-13, July.
    3. Alan A. Arslan & Yian Zhang & Nedim Durmus & Sultan Pehlivan & Adrienne Addessi & Freya Schnabel & Yongzhao Shao & Joan Reibman, 2021. "Breast Cancer Characteristics in the Population of Survivors Participating in the World Trade Center Environmental Health Center Program 2002–2019," IJERPH, MDPI, vol. 18(14), pages 1-11, July.
    4. Nedim Durmus & Yongzhao Shao & Alan A. Arslan & Yian Zhang & Sultan Pehlivan & Maria-Elena Fernandez-Beros & Lisette Umana & Rachel Corona & Sheila Smyth-Giambanco & Sharon A. Abbott & Joan Reibman, 2020. "Characteristics of Cancer Patients in the World Trade Center Environmental Health Center," IJERPH, MDPI, vol. 17(19), pages 1-15, October.
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