9/11 First Responders Show Mutations Linked to Blood Cancers

Nancy A. Melville

March 17, 2022

First responders exposed to toxic dusts and fibers in the aftermath of the World Trade Center (WTC) terror attacks show increased levels of clonal hematopoiesis linked to the development of blood cancers, new research finds. These results add to concerns about the long-term health effects of that exposure and further underscore a need for screening of those exposed.

"These data demonstrate that environmental exposure to the WTC disaster site is associated with a higher burden of clonal hematopoiesis, exceeding that expected in normal aging, and establish a rationale for mutational testing of the larger WTC-exposed population," report the authors in the study, published March 7 in Nature Medicine.

The findings come from a study of blood samples from WTC first responders, including 429 firefighters and 52 emergency medical service workers, collected between December 2013 and October 2015.

For comparisons, the authors collected blood samples from 255 firefighters from in and around Nashville, Tenn., none of whom had been exposed to the 9/11 disaster.

Genetic analysis of the samples showed that 10% of those in the WTC-exposed cohort (n = 48) had unique somatic mutations considered to likely be pathogenic, and six of those individuals carried one or more of the mutations.

After a multivariate adjustment controlling for age, sex and race/ethnicity, those among the WTC-exposed first responders had a significantly increased odds of clonal hematopoiesis versus nonexposed workers (odds ratio [OR] = 3.14; P = .0006).

The higher risk was further observed in a comparison limited only to the WTC-exposed firefighters versus nonexposed firefighters (OR = 2.93; P = .0014) after the multivariate adjustment. The greater association between WTC exposure and clonal hematopoiesis remained after the researchers controlled for smoking as well as other risk factors among the WTC-exposed group overall (OR = 3.05; P = .0015) and the firefighters-only comparison (OR = 2.78; P = .004).

A history of smoking was not significantly associated with an increased risk of clonal hematopoiesis in either model.

As a risk factor for hematologic malignancy, cardiovascular events, and mortality, "clonal hematopoiesis is a concerning acquired risk not only for diseases that are already associated with WTC exposure but also as the population ages, this may exacerbate their risk profile," Anna Nolan, coauthor of the study, and professor of medicine and environmental medicine in the division of pulmonary and critical care, New York University, said in an interview.

The most common gene mutations observed in the WTC-exposed group were those associated with myeloid malignancies, such as chronic myeloid leukemia; however, blood counts in the exposed group showed no association between exposure and mutations linked to cytopenias.

A further analysis on mice, investigating how WTC particulate matter uniquely affects DNA, surprisingly showed that just one exposure to the material was associated with clonal hematopoietic changes.

"Exposure to particulates, even at a single time point, can yield clonal mutations that may be risk for multisystem end-organ changes," Nolan said.

While the serious health effects of WTC exposure on humans, have been extensively documented, including a study published in February showing increases in skin, prostate and thyroid cancers, clonal hematopoiesis suggests further heightened risks as the exposed population grows older, Nolan noted.

"[Clonal hematopoiesis] is a concerning acquired risk not only for diseases that are already associated with WTC exposure, but also, as the population ages, this may exacerbate their risk profile," she said.

Due to the risk, "clinicians should be aware that WTC-exposed first responders have had a significant exposure and that they are at risk for developing several conditions."

Commenting on this study, William K. Oh, MD, whose team at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, has reported in a previous study on the increased risk of prostate cancer among WTC first responders, noted that more time may be necessary to better understand the full effects of the increases in clonal hematopoiesis.

"Though these findings are of concern, there were still no differences in the cohorts in actual hematologic cancers or even cytopenias, suggesting that more time and additional DNA damaging events were needed to transform the clonal hematopoiesis findings to clinically relevant diseases," Oh, clinical professor of medicine, said in an interview.

Nevertheless, "if a patient is found on testing to have clonal hematopoiesis, they should be screened more closely for blood disorders and cardiovascular issues than they might otherwise be, though this remains an area of active investigation," Oh said.

Nolan had no disclosures to report. Oh is the chief medical science officer at Sema4, a genomic testing and data company.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.


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