PROJECT SUMMARY

Our proposal aims to detect mutations associated with early signs of MDS in samples from firefighters who were exposed to the World trade center (WTC) dust after the 911 terrorist attack. The terrorist attacks on the World Trade Center (WTC) created an unprecedented environmental exposure to WTC aerosolized dust and gases that contained known and suspected carcinogens including polycyclic aromatic hydrocarbons, polychlorinated biphenyls, polychlorinated furans, dioxins and asbestos. In our sentinel study of cancer incidence following WTC exposure, we reported an excess of cancer cases in the WTC-exposed Fire Department of the City of New York (FDNY) firefighters compared with US population rates and rates in non-WTC-exposed firefighters (Zeig-Owens et al, Lancet, 2011). We continue to prospectively follow the entire FDNY cohort of firefighters for cancer incidence and have built a biorepository of samples consisting of fractionated blood components and serum from 3000+ WTC exposed FDNY subjects and non WTC exposed firefighter controls. Using this cohort, we now demonstrated a significantly higher prevalence of monoclonal gammopathy (MGUS), a precursor for multiple myeloma (Landgren, JAMA Onc, 2018). Furthermore, we have conducted targeted genome sequencing of a cohort of WTC exposed firefighters revealing a higher incidence of clonal hematopoiesis (CH) mutations and suggesting potential risk for development of myeloid neoplasms such as myelodysplastic syndromes (MDS). Based on these data, we now propose to comprehensively determine the prevalence of MDS/CH premalignant conditions in a larger cohort of WTC exposed firefighters. Early detection of these cases would enable clinical evaluation and potentially disease altering therapeutic interventions for these brave firefighters.