Prostate cancer in 9/11 responders: Study explores mechanism of action

Data from a recent study suggest that exposure to dust from the World Trade Center attack has resulted in an inflammatory cascade that led to the development of high-grade prostate cancer in first responders.

“We know from first responders and volunteers on 9/11 who were exposed to a toxic mixture of dust, that many years later, prostate cancer is one of the cancers that has shown up in increased incidence compared to age-matched, expected rates of cancer, thyroid cancer being the other cancer with clear, increased risk,” explained William Oh, MD, of the Icahn School of Medicine at Mount Sinai and Deputy Director at the Tisch Cancer Institute, New York. “What is unclear is: What is the mechanism of action? Why would breathing that dust lead to an increased risk of prostate cancer?”

Dr. Oh and colleagues conducted a two-part study that first involved looking at the prostate tissues of 15 men who were exposed to WTC dust and developed prostate cancer and compared them to matched controls of men with prostate cancer who were not exposed to WTC dust. The study was published in Molecular CancerResearch (June 20, 2019 [Epub ahead of print]).

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Looking at a panel of immune genes, Dr. Oh and colleagues found that there was a difference in the upregulation of inflammatory cells, specifically Th-17 cells, which are a subset of proinflammatory Th cell, between those men exposed to WTC dust and those not exposed to it.

“It struck us as a potential mechanism of action,” said Dr. Oh, pointing out the dust was a toxic mixture of many toxins including asbestos, polybiphenols, and hydrocarbons, and that it would be challenging to look at the impact of the individual components on prostate cancer risk or prostate cancer tissues.

In the second part of the study, Dr. Oh and colleagues used animal models to determine if exposure to the WTC dust would increase inflammation within the prostate. The animals did not have prostate cancer, noted Dr. Oh. With animals having shorter life spans, the acute and chronic effects of WTC dust can be more quickly observed than in humans, explained Dr. Oh.

“The animals were put in chambers where they were exposed to the (WTC) dust, breathed in the dust, and we looked at the impact on the prostate one day and 30 days later,” said Dr. Oh. “We found that even within 1 day of exposure, there were multiple changes in gene expression in the prostate, such that inflammatory genes are upregulated. We saw a lot of genes expressed, including genes we know are associated with an increased risk of cancer. We saw changes in prostate tissue itself."

“Inflammation is an important mechanism of cancer progression, and that was one of our hypotheses, that there would be DNA damage,” said Dr. Oh.

Continue to the next page for more.The findings are quite interesting, for they highlight how external factors can influence the risk of cancer on distant organs, according to Dr. Oh.

“It is not intuitive that the prostate would be the first organ affected (by WTC dust),” said Dr. Oh, citing organs such as the lungs that would logically be more affected.

In terms of potential therapies for these patients, immunotherapy may represent one possible treatment.

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“We only use immunotherapy when someone has metastatic cancer,” said Dr. Oh. “One of the questions we do not have the answer to is whether there are certain subtypes of prostate cancer that are more amenable to immunotherapy. We cannot say at this point if the pathway we saw upregulated (in this cohort) can be targeted with a specific drug or anti-inflammatory agent or lifestyle change.”

The findings highlight that there may be exposures or environmental risks or toxins that are not yet identified that may be putting men at risk for an inflammatory type of prostate cancer, said Dr. Oh.