Louise Gagnon

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 

“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 

Fat in abdomen, thigh linked to higher risk of aggressive prostate cancer

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.

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.

Low T could hasten time to post-RP biochemical recurrence

“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.

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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.

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

Fat deposited in sites like the abdomen and the thigh are linked to an elevated risk of aggressive 

“Previous studies of body fat and prostate cancer have focused on surrogate measures of adiposity, such as body mass index (BMI) and waist circumference,” explained Barbra Dickerman, PhD, of Harvard T.H. Chan School of Public Health in Boston.

“BMI, a measure of overall obesity, has been associated with a higher risk of advanced prostate cancer and poorer prognosis after diagnosis. Waist circumference, a measure of central adiposity, has been associated with a higher risk of advanced and high-grade prostate cancer in some, but not all, studies,” added Dr. Dickerman, working with Lorelei Ann Mucci, MPH, SCD, and colleagues.

The limitation of BMI is that it does not distinguish fat mass from lean body mass, and waist circumference does not distinguish visceral fat from subcutaneous fat, said Dr. Dickerman, noting emerging evidence points to the specific distribution of body fat as a key prognostic factor for prostate cancer outcomes.

In this particular analysis, published in 

 a total of 1,832 Icelandic men were followed for up to 13 years. In the follow-up, 172 men developed prostate cancer, and 31 died from the disease. Amongst all men, visceral fat and thigh subcutaneous fat were linked to risk of advanced and fatal disease, respectively.

“We found that the accumulation of fat in specific areas, such as visceral fat, which is deep in the abdomen surrounding the internal organs, and thigh subcutaneous fat, which is just beneath the skin, was linked to a risk of advanced and fatal prostate cancer,” said Dr. Dickerman. “The link between visceral fat and advanced and fatal prostate cancer was stronger among men with a lower BMI. Further investigation of this phenotype is required. It’s possible that greater visceral fat may be a marker for an underlying physical activity pattern or hormonal milieu which influences both fat distribution and risk of advanced disease.”

In leaner men, fat may be preferentially deposited in the visceral depot in the presence of a particular hormonal milieu.

“If this hormonal milieu is also a risk factor for advanced prostate cancer, this may partially explain the results of our analyses stratified by BMI,” said Dr. Dickerman, adding that visceral fat is inversely associated with bioavailable testosterone and adiponectin, and more strongly associated with insulin resistance and pro-inflammatory cytokines than is subcutaneous fat.

Dr. Dickerman and colleagues conducted this research in the Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study and noted the study has several strong points.

“A key strength of this study is the availability of CT (computed tomography) imaging, a gold-standard measure of body fat distribution, for more than 1,800 men who were free of cancer at baseline,” said Dr. Dickerman. “Some of the additional strengths include its population-based sample, long duration of follow-up, complete and reliable data on cancer outcomes obtained through registry linkage, and the availability of comprehensive data.”

Some of the limitations of the study include the fact that the number of advanced and fatal cancers was small, thus decreasing the study’s power, said Dr. Dickerman. Additionally, investigators did not assess changes in fat depots over time.

Prostate cancer guideline update includes genomically informed therapies

“This study supports an association between body fat distribution and prostate cancer risk,” said Dr. Dickerman, adding the findings generate hypotheses for future research on specific interventions, such as physical activity, that may target fat loss and regional fat distribution and thus benefit clinically significant prostate cancer outcomes.

More prospective studies are required to investigate fat distribution and clinically significant prostate cancer outcomes, with attention to changes in fat stores over time, taking into account potential heterogeneity by BMI, pointed out Dr. Dickerman.

“Because the study population consisted of older, white men, the results may not be generalizable to younger, more diverse groups of men,” she said.

“This study supports an association between body fat distribution and prostate cancer risk,” says researcher Barbra Dickerman, PhD.

Author | Louise Gagnon

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

Fat in abdomen, thigh linked to higher risk of aggressive prostate cancer