World Trade Center responders at higher risk for blood cancer-associated mutations, study finds
Date:
March 7, 2022
Source:
Vanderbilt University Medical Center
Summary:
Scientists determined that 9/11 first responders to the World
Trade Center have increased levels of mutations that escalate their
risk for blood cancers or cardiovascular disease, according to a
new study.
FULL STORY ========================================================================== Scientists from Vanderbilt-Ingram Cancer Center (VICC) collaborated with researchers from New York to determine that 9/11 first responders to
the World Trade Center have increased levels of mutations that escalate
their risk for blood cancers or cardiovascular disease, according to a
study published March 7 in Nature Medicine.
==========================================================================
The researchers determined that a significantly higher percentage of
World Trade Center responders have an increased mutational burden when
compared to blood sample data from BioVU, Vanderbilt's biorepository of
DNA extracted from discarded blood collected during routine clinical
testing. Among the World Trade Center firefighters, 10% had evidence
of clonal hematopoiesis compared to 6.7% for firefighters who were not
exposed to particulate matter from the burning skyscrapers. Clonal hematopoiesis is an age-associated phenomenon marked by mutations
in commonly mutated genes within blood cells that provide those
cells a competitive advantage and increases risk of blood cancer and cardiovascular disease.
The VUMC team was able to access the DNA of 203 Nashville firefighters
from BioVU. The Vanderbilt team was able to use the de-identified,
annotated data within the Synthetic Derivative (SD) to locate over
200 firefighters who were age, sex and smoking-status matched to
first responders at the World Trade Center disaster. Combined with 52 firefighters recruited at the annual convention of the International Association of Firefighters, this control group was compared to those
exposed to particulate matter at the World Trade Center disaster.
The VICC researchers were led by Michael Savona, MD, holder of the
Beverly and George Rawlings Directorship in Hematology Research,
professor of Medicine and Head of Hematology, Cellular Therapy and Stem
Cell Transplantation at VICC.
"This is the first publication that I am aware of that successfully
leveraged BioVU to measure somatic genetic changes to study clonal hematopoiesis," said Savona, one of four corresponding authors on
the study.
Alexander Silver, a MD/PhD candidate working in the Savona Lab, is one
of seven lead authors of the study.
The research team included scientists and physicians from Vanderbilt,
Albert Einstein College of Medicine, Montefiore Medical Center, the Fire Department of the City of New York Bureau of Health Services, Rutgers
Cancer Institute of New Jersey, Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, Sylvester Comprehensive Cancer Center, New York University School of Medicine, Genoptix, The Leukemia Lymphoma Society
and Dana Farber Cancer Center.
Researchers also exposed mice to World Trade Center particulate matter
thought to be equivalent to what the first responders absorbed. The
scientists observed a significant expansion of hematopoietic stem cells
30 days after exposure.
The researchers concluded that first responders to the World Trade Center
have an increased mutational burden that puts them at greater risk for
blood cancers beyond what normally occurs with aging, and further studies
of the particulate matter and the mechanism of blood cancer development
are under way.
The research work was supported by the National Institutes of Health,
The Leukemia Lymphoma Society, EvansMDS (an initiative of the Edward
P. Evans Foundation), the V Foundation for Cancer Research, the Adventure
Alle Fund, The Biff Ruttenberg Foundation, the Beverly and George Rawlings Directorship, and a gift from the Dempsey and Leinbach Families.
Other Vanderbilt authors on the study included Cosmin "Adi" Bejan, PhD, assistant professor of Biomedical Informatics, and clinical fellows in Hematology/Oncology, Shannon Stockton, MD, and Travis Spaulding, MD.
========================================================================== Story Source: Materials provided by
Vanderbilt_University_Medical_Center. Original written by Tom
Wilemon. Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Sakshi Jasra, Orsi Giricz, Rachel Zeig-Owens, Kith Pradhan, David G.
Goldfarb, Angelica Barreto-Galvez, Alexander J. Silver, Jiahao
Chen, Srabani Sahu, Shanisha Gordon-Mitchell, Gaurav S. Choudhary,
Srinivas Aluri, Tushar D. Bhagat, Aditi Shastri, Cosmin A. Bejan,
Shannon S.
Stockton, Travis P. Spaulding, Victor Thiruthuvanathan, Hiroki
Goto, Jeannine Gerhardt, Syed Hissam Haider, Arul Veerappan,
Matthias Bartenstein, George Nwankwo, Ola Landgren, Michael
D. Weiden, Jacqueline Lekostaj, Ryan Bender, Frederick Fletcher,
Lee Greenberger, Benjamin L.
Ebert, Ulrich Steidl, Britta Will, Anna Nolan, Advaitha Madireddy,
Michael R. Savona, David J. Prezant, Amit Verma. High burden
of clonal hematopoiesis in first responders exposed to the
World Trade Center disaster. Nature Medicine, 2022; DOI:
10.1038/s41591-022-01708-3 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220307132057.htm
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