Nav: Home

Inflammatory mechanisms may underlie increased risk of prostate cancer among WTC responders

June 20, 2019

Bottom Line: Inflammatory and immune-regulatory mechanisms were found to be altered in animal models and in archived prostate cancer tumor samples of responders exposed to dust from the World Trade Center terrorist attacks on Sept. 11, 2001.

Journal in Which the Study was Published: Molecular Cancer Research, a journal of the American Association for Cancer Research

Authors: 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, both in New York; and William Oh, MD, chief of the Division of Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai and deputy director at the Tisch Cancer Institute

Background: "World Trade Center responders show an overall increase in cancer incidence, including prostate cancer," said Taioli. "It is important to address the reasons for this increased incidence in order to prevent new cases in this aging cohort."

Previous work has reported an increased incidence of prostate cancer among responders to attacks on the World Trade Center. However, because these responders have been closely monitored, it remains unknown whether this increased incidence is truly related to exposure to carcinogens in the World Trade Center dust or whether it is a result of surveillance bias, noted Taioli. "Our study aimed to determine potential underlying mechanisms that could explain the link between World Trade Center responders and increased prostate cancer incidence," she said.

How the Study Was Conducted and Results: To identify differential patterns of gene expression potentially caused by exposure to World Trade Center dust, the researchers compared archived prostate cancer tumors from unexposed individuals (14 patients) and World Trade Center responders (15 patients). Prostate cancer tumors taken from 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 prostate cancer tumors taken from unexposed patients. Additionally, cell-type enrichment analyses revealed an upregulation of pro-inflammatory cell types in prostate cancer tissue samples taken from responders compared with samples taken from unexposed patients.

To understand how inhalation of World Trade Center dust may affect a healthy prostate, the researchers exposed rats to dust that was collected at Ground Zero within 72 hours after the attacks. Rats anesthetized using isoflurane received either a two-hour exposure to the dust or no exposure to the dust for two consecutive days. The dose was adjusted to mimic the level of dust first responders would have inhaled during the initial three days at Ground Zero. To identify both immediate and delayed responses to World Trade Center dust, rat prostates were harvested at one day or 30 days post exposure and analyzed.

Rat prostate samples taken after one day of exposure revealed an upregulation of pro-inflammatory cell types compared with controls. Prostate samples taken 30 days post exposure revealed an upregulation of genes involved in cholesterol biosynthesis compared with controls.

"Cholesterol is an important precursor to androgens, which are known to drive prostate cancer development," explained Oh. "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."

Author's Comments: "It has been recognized that inflammation may be an important consideration in prostate cancer progression," said Oh.

"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 pro-inflammatory cell types," noted Taioli. "This finding represents the first mechanistic link between exposure to World Trade Center dust and prostate cancer."

Oh noted, "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."

Study Limitations: Limitations of the study include a small sample size of archived human prostate samples.

Funding & Disclosures: This study was sponsored by grants from the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. Oh is a consultant/advisory board member for Sema4, CheckPoint Sciences, AstraZeneca, Sanofi, Genzyme, Bayer, and Janssen.

American Association for Cancer Research

Related Prostate Cancer Articles:

Major trial shows breast cancer drug can hit prostate cancer Achilles heel
A drug already licensed for the treatment of breast and ovarian cancers is more effective than targeted hormone therapy at keeping cancer in check in some men with advanced prostate cancer, a major clinical trial reports.
The Lancet: Prostate cancer study finds molecular imaging could transform management of patients with aggressive cancer
Results from a randomised controlled trial involving 300 prostate cancer patients find that a molecular imaging technique is more accurate than conventional medical imaging and recommends the scans be introduced into routine clinical practice.
Common genetic defect in prostate cancer inspires path to new anti-cancer drugs
Researchers found that, in prostate cancer, a mutation leading to the loss of one allele of a tumor suppressor gene known as PPP2R2A is enough to worsen a tumor caused by other mutations.
First prostate cancer therapy to target genes delays cancer progression
For the first time, prostate cancer has been treated based on the genetic makeup of the cancer, resulting in delayed disease progression, delayed time to pain progression, and potentially extending lives in patients with advanced, metastatic prostate cancer, reports a large phase 3 trial.
Men taking medications for enlarged prostate face delays in prostate cancer diagnosis
University of California San Diego School of Medicine researchers report that men treated with medications for benign prostatic hyperplasia (enlarged prostate) experienced a two-year delay in diagnosis of their prostate cancer and were twice as likely to have advanced disease upon diagnosis.
CNIO researchers confirm links between aggressive prostate cancer and hereditary breast cancer
The study has potential implications for families with members suffering from these types of tumours who are at an increased risk of developing cancer.
Distinguishing fatal prostate cancer from 'manageable' cancer now possible
Scientists at the University of York have found a way of distinguishing between fatal prostate cancer and manageable cancer, which could reduce unnecessary surgeries and radiotherapy.
Researchers find prostate cancer drug byproduct can fuel cancer cells
A genetic anomaly in certain men with prostate cancer may impact their response to common drugs used to treat the disease, according to new research at Cleveland Clinic.
ASCO and Cancer Care Ontario update guideline on radiation therapy for prostate cancer
The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario today issued a joint clinical practice guideline update on brachytherapy (internal radiation) for patients with prostate cancer.
Patient prostate tissue used to create unique model of prostate cancer biology
For the first time, researchers have been able to grow, in a lab, both normal and primary cancerous prostate cells from a patient, and then implant a million of the cancer cells into a mouse to track how the tumor progresses.
More Prostate Cancer News and Prostate Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.