First responders who worked at Ground Zero in the aftermath of the 2001 attacks on the World Trade Center in New York City were three times more likely to have genetic changes associated with an increased risk of leukemia compared with other first responders or members of the public who were not exposed to Ground Zero. Younger first responders (< age 60) who had worked at the site showed these genetic changes, which are rarely seen in people younger than age 70. Ground Zero first responders with these genetic changes have as much as a fivefold increased risk for leukemia. These study findings were presented at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 943).
“Our study has shown not only an increased risk of developing leukemia in Ground Zero–exposed first responders, but also a distinct spectrum of precancerous genetic changes in younger exposed responders,” said principal investigator Divij Verma, PhD, of Albert Einstein College of Medicine in the Bronx, New York. “We have also demonstrated that inflammation induced by exposure to toxic dust is the likely mechanism for these genetic changes, and that turning off the IL1RAP gene, in particular, may be a promising strategy to delay or inhibit the development of these genetic changes or prevent progression to leukemia.”
The genetic changes, known as clonal hematopoiesis, have no signs or symptoms and are generally detected only when a person undergoes genetic testing for another condition. Clonal hematopoiesis occurs in about 10% of people aged 70 and older, but it is rare in people younger than 70. Studies have shown that people with clonal hematopoiesis have about a 1% per year chance of developing leukemia or another hematologic malignancy; they are also at elevated risk for heart and liver diseases.
Study Details and Results
Dr. Verma and his colleagues collected blood samples from 988 firefighters and emergency medical personnel who were exposed to high levels of airborne dust, gases, and potential cancer-causing substances at Ground Zero and examined their genomes to determine how many had clonal hematopoiesis and how many of those with clonal hematopoiesis developed leukemia. On average, the blood samples were collected 10 years after exposure; at the time of the blood draw, the responders’ median age was 56. The investigators then compared the Ground Zero–exposed responders with 255 firefighters who had not been at the site but had occupational exposures to pollutants and potentially toxic substances and to 195 people from the general population who were not first responders and had not been at Ground Zero.
The investigators found that 14% of the exposed first responders had clonal hematopoiesis, compared with 7% of firefighters and other people who had not been at Ground Zero. Even though DNMT3A and TET2 were the two most common mutated genes in Ground Zero–exposed responders, the subsequent spectrum of mutations was distinct in younger Ground Zero–exposed responders (ie, those now younger than age 60) and included APC (6.6%), KMT2D (4.8%), ATM (4.8%), PIK3CA (4.2%) CREBBP (3.0%), BRCA2 (2.4%), ERBB4 (2.4%), and ARID1A (2.4%), which have not been reported in any previous studies of clonal hematopoiesis.
Of note, in the firefighters and other first responders who had no Ground Zero exposure, the risk of having clonal hematopoiesis was the same as for people who were not first responders and had not been to the site. Among Ground Zero–exposed first responders with clonal hematopoiesis, 3.7% developed leukemia, compared with 0.6% of those in the nonexposed comparison groups. Compared with exposed first responders without clonal hematopoiesis, those with clonal hematopoiesis had more genetic changes, indicating an elevated risk for leukemia or another hematologic malignancy, as well as increased levels of neutrophils and monocytes as well as red cell width suggestive of greater inflammation.
Moving Forward
All Ground Zero–exposed first responders with clonal hematopoiesis are being contacted and invited to visit the hospital to identify any health problems as early as possible and initiate treatment, if necessary, Dr. Verma said.
Dr. Verma and his team are conducting further research to identify any differences in exposures and their effects among first responders who worked at Ground Zero during the first 3 days of the disaster vs those who were there later. They are also working to identify the specific toxic components of the dust collected from Ground Zero, the mechanisms by which it causes genetic changes in exposed people, and whether these mechanisms and their effects are unique to Ground Zero exposure or have similarities with those seen in people exposed to wildfires, burn pits, and other environmental exposures.
Disclosure: This study was funded by grants from the U.S. Centers for Disease Control and Prevention and the National Institutes of Health. For full disclosure information for the study authors, visit ash.confex.com.
