Prevalence of Chronic Hematopoiesis of Indeterminate Potential (CHIP) Among WTC Responders

Details

• Personal Author:
  Boffetta P ; Mascarenhas J
• Description:
  Hematologic neoplastic and pre-neoplastic conditions are a heterogeneous group of diseases that arise from acquired genetic and epigenetic alterations in hematopoietic precursor cells. The presence of such alterations can be detected even prior to overt hematological manifestations due to increasing availability of molecular testing among individuals without over neoplastic or pre-neoplastic conditions. This finding has been defined as clonal hematopoiesis of indeterminate potential (CHIP). CHIP mutations can originate in lymphoid cells (L-CHIP) and in myeloid cells (M-CHIP). Despite the absence of detectable hematologic disorders, mutations characteristically associated with hematologic neoplasms were identified in 6 percent of individuals aged 60 years or more and associated with certain HLA types; these individuals are also at increased risk of CVD. The overarching goal of this study was to measure the prevalence of CHIP mutations in a population of WTC rescue and recovery workers, to compared the prevalence to that of subjects not exposed to WTC, and to analyze the association between CHIP mutation status and WTC exposure and other characteristics of study subjects. We analyzed samples from 357 responders recruited at the WTC Clinical Center of Excellence at Stony Brook University, of whom 130 (36.4%) were positive for CHIP mutations and 227 (63.6%) were negative. In particular, 56 responders (15.7%) were positive for M-CHIP mutations and 72 (20.2%) were positive for L-CHIP mutations. M-CHIP mutation status was associated with age (p<0.001), smoking status (p=0.02) and BMI (p=0.03). L-CHIP mutation was not associated with any of the factors under investigation. Although the prevalence of responders with cardiovascular disease was higher in responders with both MCHIP (p=0.2) and L-CHIP (p=0.4) mutations, the difference was not statistically significant. Among cardiovascular and metabolic biomarkers, carriers of M-CHIP mutations had a higher level of lymphocytes (p=0.03) and erythrocytes (p=0.04) compared to non-carriers, while no differences were observed among carriers of L-CHIP mutations. Estimated WTC exposure was not associated with either M-CHIP or L-CHIP mutation status. The prevalence of M-CHIP mutations was higher in WTC responders included in this analysis than in other populations. There are limited data in the literature on the prevalence of L-CHIP mutations. Factors associated with prevalence of M-CHIP mutations are consistent with those identified in previous studies. The lack of association with WTC exposure might be explained by low statistical power in separating exposure level of responders. In conclusion, WTC responders have a high prevalence of M-CHIP mutations which, however, does not seem to be associated with indicators of WTC exposure. [Description provided by NIOSH]
• Subjects:
  Biomarkers Cardiovascular Diseases Cardiovascular System Emergency Responders Occupational Health Safety September 11 Terrorist Attacks
• Keywords:
  Cardiovascular Disease Disaster Recovery Genetic Factors Hematopoiesis Molecular Epidemiology Rescue Workers World Trade Center WTC
• 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 ; OSHA Region 2
• 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:
  1-36
• NIOSHTIC Number:
  nn:20069595
• 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-012187, 2023 Nov; :1-36
• Contact Point Address:
  Paolo Boffetta, Stony Brook University, Cancer Center, MART building, level 7, Room 0844, Stony Brook, NY 11794
• Email:
  paolo.boffetta@stonybrookmedicine.edu
• Federal Fiscal Year:
  2024
• Performing Organization:
  State University New York Stony Brook
• Peer Reviewed:
  False
• Start Date:
  20200821
• Source Full Name:
  National Institute for Occupational Safety and Health
• End Date:
  20210630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5f5d9343b5d9e8f914306b077c18ac8022621dca6a38f6b14a07f7ce38549948abad02b049b58d295d2222a298ee39d6154e1e64ba875aa23aff2362adb66aea
• Download URL:
  https://stacks.cdc.gov/view/cdc/219244/cdc_219244_DS1.pdf
• File Type:
  [PDF - 964.65 KB ]