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Exposure to Specific Carcinogens and Prostate Cancer Risk Among World Trade Center First Responders

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Key Points

  • Prostate cancer diagnosed in first responders to the attack on the World Trade Center has a distinct gene-expression pattern that may be the result of exposure to specific carcinogens in the dust from the fallen buildings.
  • The prostate of the animal models exposed to World Trade Center dust displayed unique changes in gene expression and immune cell infiltrates, suggesting that the effect of exposure may be measured locally in target organs.
  • Inflammation from exposure to environmental particulates could be the common pathway driving an increase in cancer occurrence.

Since the attacks on the World Trade Center on September 11, 2001, studies have shown an increased risk of several cancers—including multiple myeloma and prostate, head and neck, and thyroid cancers—among first responders to the scene. The results from a new study by Gong et al published in Molecular Cancer Research may explain the cause of an increased risk of prostate cancer among these first responders. According to the study findings, inflammatory mechanisms activated in the prostate after exposure to the carcinogens and tumor-promoting agents contained in the dust from the fallen World Trade Center towers may be responsible for that increased risk.

Study Methods

To identify differential patterns of gene expression potentially caused by exposure to dust from the World Trade Center, the researchers compared archived prostate cancer tumors from 15 unexposed non–World Trade Center patients and 15 World Trade Center responders obtained from the Mount Sinai tumor bank. The two cohorts were matched for age, race/ethnicity, and Gleason scores.

The investigators studied the immunologic and inflammatory cascade in the archived prostate cancer tissues of the World Trade Center patients using a digital gene-expression assay, in comparison with the unexposed prostate cancer cases. In addition, the researchers performed RNA sequencing in rats to understand the immediate and delayed responses of healthy prostate tissue to acute World Trade Center dust inhalation.

Results

The researchers found the prostate cancer tumors from the responders showed a downregulation of genes involved in immune-cell chemotaxis and proliferation and an upregulation of genes involved in apoptosis and immune modulation compared with the prostate cancer tumors taken from the unexposed patients. In addition, cell-type enrichment analyses found an upregulation of proinflammatory cell types in prostate cancer tissue samples taken from the responders compared with the samples taken from the unexposed patients.

The rat prostate samples taken after 1 day of exposure to the World Trade Center dust revealed an upregulation of proinflammatory cell types compared with the controls. Prostate samples taken 30 days postexposure revealed an upregulation of genes involved in cholesterol biosynthesis compared with the controls.

“Cholesterol is an important precursor to androgens, which are known to drive prostate cancer development,” said William K. Oh, MD, Chief of the Division of Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai, New York, and principal investigator of this study, in a statement. “Our preliminary finding that exposure to World Trade Center dust increased the expression of genes in the cholesterol biosynthesis pathway highlights an additional mechanism by which environmental exposures may lead to the progression of prostate cancer…. Our results suggest that inflammatory mechanisms are activated in the prostate after exposure to World Trade Center dust, which may give rise to chronic inflammation and contribute to prostate cancer progression.”

These results may also have implications for the greater population exposed to environmental particulates, such as emissions from motor vehicles, industrial processes, power generation, and the household combustion of solid fuel, because inflammation could be the common pathway driving an increase in the development of cancer.

Dr. Oh is the corresponding author of this study.

Disclosure: Funding for this study was provided by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. For full disclosures of the study authors, visit mcr.aacrjournals.org.

 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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