If you were there at Ground Zero in New York City on 9/11, you breathed it in. If you were in one of the World Trade Center towers when it happened, or a first responder on the scene soon afterward, you breathed in more of it. And because of that, if you are a man, you now have a higher risk of developing aggressive prostate cancer.
What was in the air that day, as jets burned and the towers fell? Basically, in all the devastation, a terrible dust cloud was unleashed: a vile, noxious brew of soot, benzene, asbestos, cement, PCBs, PAHs, dioxin, and other toxic agents. Individually, many of these are known carcinogens. Together, these foul ingredients acted like lighter fluid for inflammation in those exposed to them. And guess where the Ground Zero for inflammation seems to be in men? The prostate.
“The dust was an inflammatory insult to the body,” says medical oncologist William Oh, M.D., of the Icahn School of Medicine at Mount Sinai in New York. Oh and Mount Sinai epidemiologist Emanuela Taioli, M.D., Ph.D., recently published a study in Molecular Cancer Research showing that one of the inflammatory responses within the prostate was an increase in an inflammatory T cell, called Th-17, in men exposed to the toxic dust. Oh believes that exposure to the toxins “increased the inflammatory cascade within the prostate, and this may have contributed to the risk of developing more aggressive prostate cancer,” particularly in first responders and volunteers who spent a lot of time searching for victims in the rubble.
Now, you may be wondering: If men who were at Ground Zero develop prostate cancer, how do scientists like Oh know whether it’s because of something they were exposed to there, or whether they were likely to develop prostate cancer anyway? “Many of the first responders were men in their 50s, 60s, and even 70s who might have been at risk of prostate cancer already, so we didn’t look at diagnoses of prostate cancer in the first years after 9/11,” Oh explains. “But now, almost 20 years later, it is clear that the incidence of prostate cancer – and the difference between those who were exposed to the dust and age-matched men who were not exposed – is significantly higher in the World Trade Center first responders and volunteers. We are seeing continued evidence of prostate cancer diagnosis and progression that’s higher than expected, and also more aggressive.”
How could they be sure this cancer was somehow linked to exposure to the awful dust? “We took some of the material that was collected a few days after 9/11, and exposed rats to it in sealed air chambers,” says Oh. “The rats were exposed to the dust and they inhaled the dust.” Then Oh and colleagues looked at the rats’ prostates at various time points afterward. “After just a few hours of exposure, within a day, and within a month, there was an increase in inflammation in the rat prostate. Just after inhaling the World Trade Center dust, they had increased inflammation in their prostates.”
In another study, when they compared the prostate cancers in the men who were at Ground Zero to a control group of men with prostate cancer who had not been exposed to the dust, “we saw the same inflammatory pathways,” says Oh. This finding suggests the 9/11 dust may simply have followed a route commonly used by prostate cancer – and hit the accelerator, so cancer developed over the course of years instead of decades.
Oh and colleagues also noticed something else very interesting in comparing the healthy rats that were exposed to the World Trade Center dust with other healthy rats: statistically significant genetic differences in the cholesterol pathway. The rats exposed to the dust had “upregulated genes in their prostate associated with cholesterol metabolism. What’s curious about this is that the cholesterol pathway is associated with precursors that lead to androgen,” male hormones that drive the growth of prostate cancer. Exactly how this pathway may drive prostate cancer is the subject of future research. The scientists also saw an increase in some of the more commonly known genes involved in prostate cancer, particularly genes involved in DNA damage repair.
What is it about inflammation that leads to the development of cancer? “We’ve all had inflammation,” says Oh. “When we get a cut, our skin turns red and gets swollen, because the body’s trying to fight bacteria and prevent infection. That’s a good type of inflammation. Sometimes, though, inflammation may actually stimulate the growth of cancer. There’s a long history of knowing that people who have tuberculosis can get a scar in an area of their lung, and sometimes will develop cancer in that area. Sometimes inflammation can stimulate the growth of some cancers. This is where inflammation may be dysfunctional and negative.”
Oh became interested in the link to inflammation after seeing certain changes in some of his patients: For example, “One of my patients, a young man in his 30s, a police officer, was a first responder on 9/11. Within a few years, he started having a lot of lower urinary tract symptoms – frequency of urination, burning. He developed prostate cancer in his 40s. Did the exposure somehow change the body’s inflammatory state, to increase either the risk or the nature of the cancer they developed?”
Although the men exposed to the dust tend to develop cancer at an earlier age and to have a more aggressive form, there is reassuring news: “This cancer seems to be just as curable as any other prostate cancer if it’s caught early. There’s no evidence that, stage for stage, the outcomes are not just as good as in any other man.”
The PCF is actively funding research into the role of inflammation in prostate cancer, and how environmental exposures to toxic chemicals such as Agent Orange and battlefield chemicals can lead to prostate cancer.
“What we learn from these men can have extraordinary implications,” says medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of the PCF.
“Sometimes, great medical detective work in human tragedy can save thousands of lives later on. Seeing how the environmental exposure at Ground Zero accelerated prostate cancer in these men can help us learn how to stop it in the first place. That is how asbestos and mesothelioma came together in mine workers to open up our understanding of how to treat that form of lung cancer. What William Oh and colleagues are learning now, in a relatively few men, might one day lead to treatments that can help everybody.”