Global DNA methylation of WTC prostate cancer tissues show signature differences compared to non-exposed cases.

Details

• Personal Author:
  Aaronson SA ; Alpert N ; Donovan M ; Gong Y ; Mulholland DJ ; Oh WK ; Taioli E ; Tuminello S ; van Gerwen M ; Wang L ; Yoo S ; Yu H ; Zhu J
• Description:
  There is increased incidence of prostate cancer (PC) among World Trade Center (WTC)-exposed responders and community members, with preliminary evidence suggestive of more aggressive disease. While previous research is supportive of differences in DNA methylation and gene expression as a consequence of WTC exposure, as measured in blood of healthy individuals, the epigenetics of WTC PC tissues has yet to be explored. Patients were recruited from the World Trade Center Health Program. Non-WTC PC samples were frequency matched on age, race/ethnicity and Gleason score. Bisulfite-treated DNA was extracted from tumor tissue blocks and used to assess global DNA methylation with the MethylationEPIC BeadChip. Differential and pathway enrichment analyses were conducted. RNA from the same tumor blocks was used for gene expression analysis to further support DNA methylation findings. Methylation data were generated for 28 samples (13 WTC and 15 non-WTC). Statistically significant differences in methylation were observed for 3,586 genes; on average WTC samples were statistically significantly more hypermethylated (P = 0.04131). Pathway enrichment analysis revealed hypermethylation in epithelial mesenchymal transition (EMT), hypoxia, mitotic spindle, TNFA signaling via NFKB, WNT signaling, and TGF beta signaling pathways in WTC compared to non-WTC samples. The androgen response, G2M and MYC target pathways were hypomethylated. These results correlated well with RNA gene expression. In conclusion, long-term epigenic changes associated with WTC dust exposure were observed in PC tissues. These occurred in genes of critical pathways, likely increasing prostate tumorigenesis potential. This warrants analysis of larger WTC groups and other cancer types. [Description provided by NIOSH]
• Subjects:
  Carcinogens Emergency Responders Genetics Occupational Health Safety September 11 Terrorist Attacks
• Keywords:
  World Trade Center; WTC; Prostate cancer; Carcinogenesis; Emergency responders; Genetics; DNA damage; Gene expression; Genes; Signaling pathways
• ISSN:
  0143-3334
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• 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:
  43
• Issue:
  6
• NIOSHTIC Number:
  nn:20065503
• Citation:
  Carcinogenesis 2022 Jun; 43(6):528-537
• Contact Point Address:
  Emanuela Taioli, Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
• Email:
  emanuela.taioli@mountsinai.org
• Federal Fiscal Year:
  2022
• Performing Organization:
  Icahn School of Medicine at Mount Sinai, New York
• Peer Reviewed:
  True
• Start Date:
  20160901
• Source Full Name:
  Carcinogenesis
• End Date:
  20210831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:62a961bfdd823d7b8c7850afb6a68d117fb256e9109659ba6ee16c3f103f55516e7c50d9dde277c30e136e8bc11e824fc7b80606fc0d5607305f2ab1a2d33921
• Download URL:
  https://stacks.cdc.gov/view/cdc/248683/cdc_248683_DS1.pdf
• File Type:
  [PDF - 11.97 MB ]