Project Summary/Abstract Hazardous materials including known and suspected carcinogens, were present at the World Trade Center (WTC) disaster site.1,2 For example, some carcinogens present at the WTC disaster site have been found to be associated with multiple myeloma and its precursor disease, in veterans of the Vietnam War exposed to Agent Orange. Recently, in a screening study for multiple myeloma precursor disease, the prevalence of overall monoclonal gammopathy of undetermined significance (MGUS) among WTC-exposed white male firefighters was significantly greater than the general population (risk ratio [RR]=1.76; 95% CI=1.34, 2.29).3 This association was particularly elevated in light-chain MGUS (RR=3.13; 95% CI=1.99, 4.93).3 Additionally, WTC- exposed firefighters compared with the general population had higher proportions with light chain disease and CD20 positive plasma cells, which are typically associated with poorer prognoses.3 In an effort to broaden current knowledge of the relationship between WTC exposure, MGUS and multiple myeloma, we propose a collaborative effort between the Fire Department of the City of New York (FDNY) and General Responder Cohort at Stony Brook University (GRC-SBU) to conduct sensitive immunophenotyping to detect MGUS by screening non-FDNY rescue-recovery workers and comparing results to determine if there are differences between the two responder cohorts. We will then pool data from the two cohorts to generate a global prevalence estimate for the entire WTC-exposed rescue-recovery population. By expanding MGUS screening beyond white male firefighters, we will assess whether the association between WTC exposure and MGUS applies to a more demographically heterogeneous population. Additionally, this will provide us with a better understanding of the disease pathogenesis in participants exposed to the WTC disaster. Finally, an early workup of MGUS can provide potentially disease-modifying therapeutic interventions. This study will allow us to realize the NIOSH WTC Health Program's “Research to Care” translational model. Specifically we aim to 1) To analyze the precursor state of multiple myeloma, MGUS, among WTC-exposed GRC-SBU participants and to compare the prevalence among white males to WTC-exposed white male FDNY firefighters; and 2) To compare the prevalence of MGUS among the combined WTC-exposed responder cohorts (both FDNY and GRC-SBU) to published estimates in population-based studies.