Genome-Wide DNA Methylation Profiles and Breast Cancer Among World Trade Center Survivors

Details

• Personal Author:
  Arslan AA ; Ashebir YA ; Chen Y ; Durmus N ; Ramaswami S ; Reibman J ; Schroff C ; Shao Y ; Snuderf M ; Tuminello S
• Description:
  Background: Increased incidence of cancer has been reported among World Trade Center (WTC)-exposed persons. Aberrant DNA methylation is a hallmark of cancer development. To date, only a few small studies have investigated the relationship between WTC exposure and DNA methylation. The main objective of this study was to assess the DNA methylation profiles of WTC-exposed community members who remained cancer free and those who developed breast cancer. Methods: WTC-exposed women were selected from the WTC Environmental Health Center clinic, with peripheral blood collected during routine clinical monitoring visits. The reference group was selected from the NYU Women's Health Study, a prospective cohort study with blood samples collected before 9 November 2001. The Infinium MethylationEPIC array was used for global DNA methylation profiling, with adjustments for cell type composition and other confounders. Annotated probes were used for biological pathway and network analysis. Results: A total of 64 WTC-exposed (32 cancer free and 32 with breast cancer) and 32 WTC-unexposed (16 cancer free and 16 with prediagnostic breast cancer) participants were included. Hypermethylated cytosine-phosphate-guanine probe sites (defined as β > 0.8) were more common among WTC-exposed versus unexposed participants (14.3% vs. 4.5%, respectively, among the top 5000 cytosine-phosphate-guanine sites). Cancer-related pathways (e.g., human papillomavirus infection, cGMP-PKG) were overrepresented in WTC-exposed groups (breast cancer patients and cancer-free subjects). Compared to the unexposed breast cancer patients, 47 epigenetically dysregulated genes were identified among WTC-exposed breast cancers. These genes formed a network, including Wnt/ β-catenin signaling genes WNT4 and TCF7L2, and dysregulation of these genes contributes to cancer immune evasion. Conclusion: WTC exposure likely impacts DNA methylation and may predispose exposed individuals toward cancer development, possibly through an immune-mediated mechanism. [Description provided by NIOSH]
• Subjects:
  Cohort Studies Environmental Exposure Epidemiology Occupational Health Safety September 11 Terrorist Attacks
• Keywords:
  Author Keywords: Breast Cancer Breast Cancer Cohort Studies DNA Damage DNA Methylation Environmental Exposure Epigenetics World Trade Center WTC
• ISSN:
  2474-7882
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  8
• Issue:
  3
• NIOSHTIC Number:
  nn:20069869
• Citation:
  Environ Epidemiol 2024 Jun; 8(3):e313
• Contact Point Address:
  Alan A. Arslan, Department of Population Health, NYU Grossman School of Medicine, 180 Madison Avenue, New York, NY 10016
• Email:
  Alan.Arslan@nyulangone.org
• Federal Fiscal Year:
  2024
• Performing Organization:
  New York University School of Medicine
• Peer Reviewed:
  True
• Start Date:
  20210701
• Source Full Name:
  Environmental Epidemiology
• End Date:
  20230630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:78f1d3d4274643686c4ee22a32ffe44999ea2dae3b7c959492a32fb7a33f6c80745ae6a972985a9b5e94588580adf5648e2ce509c12459b121ddc6b85bf7a535
• Download URL:
  https://stacks.cdc.gov/view/cdc/208209/cdc_208209_DS1.pdf
• File Type:
  [PDF - 1.26 MB ]