Early Detection of Clonal Hematopoiesis and Leukemia Associated Mutations in WTC Exposed Firefighters After the 9/11 Attacks

Details

• Personal Author:
  Verma AK
• Description:
  To comprehensively determine the association between WTC exposure and CH, we conducted a sequencing analysis of a larger cohort of FDNY-WTC-responders including younger, exposed individuals, and two non-WTC-exposed comparison populations. Importantly, the inclusion of a larger proportion of younger WTC-exposed responders reflects the diverse demographic profile of people and rescue workers affected by this and other environmental disasters. We evaluated CH status in FDNY responders who were exposed to the WTC disaster (n=988; 912 firefighters, 76 EMS) and non- WTC-exposed firefighters (n=255) and non-WTC-exposed controls (n=195). The majority of participants across both WTC-exposed and non-WTC-exposed groups were male (98.1%) and identified as White (88.3%). This cohort is predominantly composed of younger WTC-exposed responders, with 81% being under the age of 60. WTC-exposed responders. Each participant had bulk DNA isolated from their total blood which was used for deep targeted sequencing of 237 genes frequently mutated in hematologic malignancies in a clinical grade CLIA certified lab. Clinically significant somatic mutations with a variant allele frequency (VAF) between 2% and 40% were designated as somatic mutations indicative of CH. Furthermore, CH mutations were annotated as significant based on reference databases, including the Catalog of Somatic Mutations in Cancer (COSMIC), dbSNP database, and Exome Aggregation Consortium (ExAC). In the WTC-exposed cohort, we identified 136 individuals with 165 total somatic mutations of expected pathogenic potential for an overall prevalence of 13.8%. Of those with CH, 22 individuals (22/136, 16%) carried more than one CH mutation. The prevalence of CH was 6.7% (17/255) in the non-WTC-exposed firefighters and 7.2% (14/195) in the non-WTC-exposed controls; the prevalence of CH was similar between these two control groups. Four individuals (4/17, 23%) in the non-WTC-exposed firefighter group and two individuals (2/14, 14%) in the non-WTC-exposed control group carried more than one CH mutation. Among both the WTC-exposed cohort and the non-WTC-exposed cohorts, the crude age-specific prevalence CH increased with age (Fig. S1A). We conducted multivariable logistic regression analyses to determine the association between WTC exposure and CH status controlling for age, sex and race/ethnicity. In these analyses, we restricted the logistic models to those older than 50 due to sparse data in both of the comparison populations. In models comparing WTC-exposed responders with non-WTC-exposed firefighters, WTC exposure was associated with over a 3-fold increased odds of CH (OR, 3.38; 95% CI, 1.90-6.34; P<0.01) (Fig. S1B). Similarly in models comparing the WTC-exposed responders with non-WTC-exposed controls, WTC exposure was associated with a 3.5 fold increase in CH (OR, 3.57; 95% CI, 1.94-7.01; P<0.01) (Fig. S1B). Among the WTC-exposed cohort, with each subsequent decade, we noted a significant increase in the prevalence of pathogenic somatic mutations (OR=1.23 for each increase in age group decile (95% CI: [1.00, 1.50]); P=0.048)). There was no difference of CH burden when comparing control groups non-WTC-exposed firefighters with non-WTC-exposed controls (OR, 0.95; 95% CI, 0.45-1.97; P=0.88) (Fig. S1B). In multivariable analyses restricted to those with smoking information, when controlling for smoking as well as age, sex and race/ethnicity, the association between WTC-exposure and CH remained (OR=3.37, 95% CI: 1.85-6.49, P<0.01 for WTC-exposed responders vs non-WTC exposed firefighters and OR=3.58, 95% CI: 1.94-7.04, P<0.01 for WTC-exposed responders vs the non-WTC-exposed controls). Smoking history was not significantly associated with CH in either multivariable model. [Description provided by NIOSH]
• Subjects:
  Cohort Studies Firefighters Genetics Occupational Health Particulate Matter Safety September 11 Terrorist Attacks
• Keywords:
  Cohort Studies DNA Damage Fire Fighters Gene Mutation Genes Genomics Genotoxicity Hematopoiesis Particulates World Trade Center WTC

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• Series:
  Grant Final Reports
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Final Cooperative Agreement Report
• Place as Subject:
  New York ; New York City Region [OSHA]
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OEP - Office of Extramural Programs
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-11
• NIOSHTIC Number:
  nn:20070828
• Citation:
  Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, U01-OH-012271, 2025 Jan; :1-11
• Email:
  amit.verma@einsteinmed.org
• Federal Fiscal Year:
  2025
• Performing Organization:
  Albert Einstein College of Medicine, Bronx, New York
• Peer Reviewed:
  False
• Start Date:
  20210701
• Source Full Name:
  National Institute for Occupational Safety and Health
• End Date:
  20240630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:65a050c118f365f4f7940e6e443d73fd5e3f4cae5ab27650bef0ac99b39dd84807994fbff23a2c8185c580b86df9a3d672376bc145e1c0659d5dfe07c2b5cc69
• Download URL:
  https://stacks.cdc.gov/view/cdc/219285/cdc_219285_DS1.pdf
• File Type:
  [PDF - 197.86 KB ]