High burden of clonal hematopoiese in first responders exposed to the World Trade Center disaster

The terrorist attacks on the World Trade Center created an unprecedented environmental exposure to aerosoled dust, gases, and potential carcinogens. Clonal hematopoiesis (CH) is defined as the acquisition of somatic mutations in blood cells, and is associated with smoking and exposure to genotoxic stimuli. Deep targeted sequencing of blood samples identified a significantly higher proportion of WTC-exposed first responders with CH (48 out of 481; 10%) when compared to non-WTC-exposed firefighters (17 out of 255; 6.7%; OR 3.14; p=0.0006) after controlling for age, sex, and race/ethnicity. The frequency of somatic mutations in WTC-exposed first responders showed an age-related increase, and predominantly affected DNMT3A, TET2, and other CH-associated genes.