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‘First mechanistic link’ observed between World Trade Center dust exposure, prostate cancer
Changes in inflammatory and immune regulatory mechanisms after exposure to World Trade Center dust may drive prostate cancer progression among 9/11 responders, according to study results published in Molecular Cancer Research.
“We know that prostate cancer is one of the cancers that clearly seems to be increased in World Trade Center first responders; the mechanism is unclear, because there are some cancers that don’t seem to be increased,” William Oh, MD, chief of the division of hematology and medical oncology at Icahn School of Medicine at Mount Sinai and deputy director at Tisch Cancer Institute, said in an interview with HemOnc Today. “I would see some of these patients in my clinic, and one thing that struck me was that there was an increased number of younger men, and at least a few of them had these antecedent inflammatory symptoms.”
Oh and colleagues assessed expression of immunologic and inflammatory genes in archived prostate cancer tumors collected from 15 World Trade Center responders (mean age, 54.7 years; 53.3% white) and 14 nonresponders (mean age, 55.07 years; 85.7% white). Patients in the groups had similar Gleason scores.
nonresponders.
Cell-type enrichment analysis revealed significant upregulation of three cell types in 9/11 responders’ tumors: CD56(bright), a subset of natural killer cells; total natural killer cells; and Th17 cells, a subset of proinflammatory Th cells.
To study the effects of World Trade Center dust inhalation on a healthy prostate, the researchers exposed anesthetized rats to dust taken from ground zero within 72 hours of the attacks. Exposure occurred for 2 hours on 2 consecutive days, with the dose adjusted to replicate the level of dust first responders would have inhaled during the first 3 days at ground zero. Rats that received no exposure to the dust served as controls.
The researchers performed RNA sequencing on the rat prostates, harvested at 1 day or 30 days post-exposure, to examine both the immediate and delayed effects of the dust.
“The relationship between cholesterol and prostate cancer is an intriguing one, because we know there may be dietary causes underlying prostate cancer in general,” Oh told HemOnc Today. “Also, cholesterol is a precursor to androgen production, and androgens are a known driver of prostate cancer.”
Oh said future studies will evaluate the effects of the ground zero dust on mouse models of prostate cancer. He said the dust was collected in the days following the 9/11 attacks in response to a mandate by federal authorities.
“They collected the dust in order to be sure that studies could be done on this in the future,” he said. “It was quite insightful.”
Emanuela Taioli, MD, PhD, director of the Institute for Translational Epidemiology at the Icahn School of Medicine at Mount Sinai and associate director for Population Science at the Tisch Cancer Institute, the study advances the current knowledge of the effects of exposure to dust at ground zero.
“In our study, both the archived human prostate cancer tissues of 9/11 responders and the prostates of rats experimentally exposed to World Trade Center dust showed an increase in proinflammatory cell types,” Taioli said in a press release. “This finding represents the first mechanistic link between exposure to World Trade Center dust and prostate cancer.” – by Jennifer Byrne
For more information:
William Oh, MD , can be reached at Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029; email: william.oh@mssm.edu.
Disclosures: Oh reports consultant/advisory roles with AstraZeneca, Bayer, CheckPoint Sciences, Genzyme, Janssen, Sanofi and Sema4. One other author reports consultant/advisory roles with AstraZeneca, Bristol-Myers Squibb, Dracen, Dragony, Merck and Pzer.