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Mol Cancer Res. 2019 Jun 20. doi: 10.1158/1541-7786.MCR-19-0115. [Epub ahead of print]

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

Author information

1
Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
2
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
3
Sema4, a Mount Sinai Venture, Stamford, Connecticut.
4
Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, New York.
5
Nelson Institute of Environmental Medicine, New York University, Tuxedo Park, New York.
6
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
7
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
8
Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, New York. william.oh@mssm.edu emanuela.taioli@mountsinai.org.
9
Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York. william.oh@mssm.edu emanuela.taioli@mountsinai.org.
#
Contributed equally

Abstract

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 acute WTC 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.Visual Overview: http://mcr.aacrjournals.org/content/early/2019/06/18/1541-7786.MCR-19-0115/F1.large.jpg.

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