Prostate Cancer in World Trade Center Responders Demonstrates Evidence of an Inflammatory Cascade

Details

• Personal Author:
  Aaronson SA ; Alpert N ; Chen L-C ; Cohen MD ; Donovan MJ ; Galsky M ; Gong Y ; Hashim D ; Horton L ; Lee H-W ; Oh WK ; Park S-H ; Prophete C ; Sisco M ; Suarez-Farinas M ; Taioli E ; Wang L ; Yu H ; Zelikoff J ; Zhu J
• Description:
  An excess incidence of prostate cancer has been identified among World Trade Center (WTC) responders. In this study, we hypothesized that WTC dust, which contained carcinogens and tumor-promoting agents, could facilitate prostate cancer development by inducing DNA damage, promoting cell proliferation, and causing chronic inflammation. We compared expression of immunologic and inflammatory genes using a NanoString assay on archived prostate tumors from WTC Health Program (WTCHP) patients and non-WTC patients with prostate cancer. Furthermore, to assess immediate and delayed responses of prostate tissue to acuteWTC dust exposure via intratracheal inhalation, we performed RNA-seq on the prostate of normal rats that were exposed to moderate to high doses of WTC dust. WTC prostate cancer cases showed significant upregulation of genes involved in DNA damage and G2-M arrest. Cell-type enrichment analysis showed that Th17 cells, a subset of proinflammatory Th cells, were specifically upregulated in WTC patients. In rats exposed to WTC dust, we observed upregulation of gene transcripts of cell types involved in both adaptive immune response (dendritic cells and B cells) and inflammatory response (Th17 cells) in the prostate. Unexpectedly, genes in the cholesterol biosynthesis pathway were also significantly upregulated 30 days after acute dust exposure. Our results suggest that respiratory exposure to WTC dust can induce inflammatory and immune responses in prostate tissue. Implications: WTC-related prostate cancer displayed a distinct gene expression pattern that could be the result of exposure to specific carcinogens. Our data warrant further epidemiologic and cellular mechanistic studies to better understand the consequences of WTC dust exposure. [Description provided by NIOSH]
• Subjects:
  Dust Emergency Responders Genetics Neoplasms Occupational Health Safety September 11 Terrorist Attacks
• Keywords:
  Cancer Cell Proliferation Chronic Inflammation DNA Damage Dust Exposure Emergency Responders First Responders Genes World Trade Center WTC
• ISSN:
  1541-7786
• Document Type:
  Text
• Funding:
  Cooperative Agreement ; Grant
• Genre:
  Journal Article
• Place as Subject:
  Connecticut ; New York ; OSHA Region 1 ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  17
• Issue:
  8
• NIOSHTIC Number:
  nn:20056257
• Citation:
  Mol Cancer Res 2019 Aug; 17(8):1605-1612,1774
• Contact Point Address:
  William K. Oh, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029
• Email:
  william.oh@mssm.edu
• Federal Fiscal Year:
  2019
• Performing Organization:
  Icahn School of Medicine at Mount Sinai, New York
• Peer Reviewed:
  True
• Start Date:
  20130701
• Source Full Name:
  Molecular Cancer Research
• End Date:
  20170630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0746f5259abdaab64cc0c28b9bb4418b40493e9ef556af8f4c907bb09dd5f383adc0b32e147da934fe2cb65385ae786d968103f2ed8c06e799d5cd2e5316f0b0
• Download URL:
  https://stacks.cdc.gov/view/cdc/213898/cdc_213898_DS1.pdf
• File Type:
  [PDF - 1.02 MB ]