A recent update of cancer incidence among members of the WTC General Responders Cohort (GRC) indicates an increased incidence of hematologic neoplasms, and specifically leukemia. Leukemia and other hematologic neoplasms are a heterogeneous group of cancers that arise from acquired genetic and epigenetic alterations in hematopoietic precursor cells. The presence of alterations in key genes can be detected prior to overt hematological manifestations due to increasing availability of molecular testing among individuals who do not yet meet the diagnostic criteria for a hematologic neoplasm. The detection of mutated clones in healthy individuals has been defined as clonal hematopoiesis of indeterminate potential (CHIP). Mutations characteristically associated with hematologic neoplasm risk were identified in 4 percent of those aged 60 or more; these individuals are also at increased risk of cardiovascular disease. The overarching aim of this study is to determine whether WTC exposed subjects have an increased prevalence of CHIP, to test the hypothesis that CHIP-specific mutations will be detected in a subgroup of healthy WTC responders, allowing earlier identification of a subpopulation at higher risk for developing hematologic neoplasms and cardiovascular disease.
In Specific Aim 1 we plan to determine the prevalence of CHIP in 350 WTC responders, and to compare it with unexposed controls.
In Specific Aim 2 we plan to investigate the association between prevalence of CHIP and cardiovascular biomarkers, risk factors and risk scores in WTC responders.
In Specific Aim 3, we plan to investigate the association between prevalence of CHIP and quantitative measures of WTC exposure. The integration of the results would lead to the identification of WTC responders at high risk of CHIP- related conditions, who might be subjects to enhanced medical surveillance.

Public Health Relevance

World Trade Center (WTC) responders experienced an increased risk of leukemia and cardiovascular disease. We plan to study the prevalence of clonal hematopoiesis of indeterminate potential (CHIP), an asymptomatic condition entailing an increased risk of leukemia and cardiovascular disease, among 350 healthy WTC responders and a group of controls. These results will lead to strategies to prevent leukemia and cardiovascular disease in WTC responders.

National Institute of Health (NIH)
National Institute for Occupational Safety and Health (NIOSH)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZOH1)
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Yiin, James
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Icahn School of Medicine at Mount Sinai
Internal Medicine/Medicine
Schools of Medicine
New York
United States
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