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

Jasra, Sakshi; Giricz, Orsi; Zeig‐Owens, Rachel; Pradhan, Kith; Goldfarb, David G.; Barreto-Galvez, Angelica; Silver, Alexander J.; Sahu, Srabani; Gordon-Mitchell, Shanisha; Choudhary, Gaurav S.; Aluri, Srinivas; Bhagat, Tushar D.; Shastri, Aditi; Bejan, Adrian; Stockton, Shannon; Spaulding, Travis; Thiruthuvanathan, Victor; Goto, Hiroki; Gerhardt, Jeannine; Haider, Syed Hissam; Veerappan, Arul; Bartenstein, Matthias; Nwankwo, George; Landgren, Ola; Weiden, Michael D.; Lekostaj, Jacqueline K.; Bender, Ryan; Fletcher, Frederick A.; Greenberger, Lee M.; Ebert, Benjamin L.; Steidl, Ulrich; Will, Britta; Nolan, Anna; Madireddy, Advaitha; Savona, Michael R.; Prezant, David J.; Verma, Amit

doi:10.1038/s41591-022-01708-3

Cited by 27 publications

(13 citation statements)

References 20 publications

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“…Further molecular and mutational signature analysis of the tumors of these women may identify distinct genetic signatures. Recently, Jasra and colleagues [36] exposed mice to WTC particulate matter and the hematopoietic stem cells were collected, revealing murine mutational signatures closely related to COSMIC signatures associated with tobacco smoke. They also noted an increased burden of clonal hematopoiesis in first responders with WTC exposure compared to non-WTC exposed firefighters suggesting a link between WTC dust exposure with increased genotoxic stress and inflammation [36].…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Women with Lung Adenocarcinoma in the World Trade Center Environmental Health Center

Shum

Durmuş

Pehlivan

et al. 2022

IJERPH

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The destruction of the World Trade Center towers on 11 September 2001 exposed local residents, workers, and individuals in the area (Survivors) to dust and fumes that included known and suspected carcinogens. Given the potential for inhalation of toxic substances and the long latency after exposure, the incidence of lung cancer is expected to increase in WTC-exposed individuals. We describe the characteristics of women WTC Survivors with lung adenocarcinoma who were enrolled in the WTC Environmental Health Center (WTC EHC) between May 2002 and July 2021. A total of 173 women in WTC EHC had a diagnosis of any type of lung cancer, representing 10% of all cancers in women. Most of the lung cancers (87%) were non-small cell carcinomas, with adenocarcinoma (77%) being the most common subtype. Nearly half (46%) of these patients were exposed to dust clouds on 11 September 2001. Race and ethnicity varied by smoking status, as follows: 44% of Asian women compared with 29% of non-Hispanic White women were never-smokers (p < 0.001). There was no significant difference between the pathologic characteristics of adenocarcinomas between never and ever smokers. We also summarize EGFR, ALK, KRAS, ROS-1 and BRAF mutation status stratified by smoking, race and ethnicity. The identification of a relatively high proportion of women never-smokers with lung cancer warrants further investigation into the role of WTC dust exposure.

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Section: Discussionmentioning

confidence: 99%

Characteristics of Women with Lung Adenocarcinoma in the World Trade Center Environmental Health Center

Shum

Durmuş

Pehlivan

et al. 2022

IJERPH

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“…Exposure to elevated levels of PAHs based on levels of PAH-DNA adducts in cord blood may have contributed to reduced fetal growth ( Perera et al, 2005 ) and a modest reduction in cognitive development among children exposed prenatally to WTC dust ( Perera et al, 2007 ). Relative to non-WTC-exposed firefighters, DNA sequence analysis of blood from WTC first responders showed increased clonal hematopoiesis, which is the acquisition of somatic mutations in blood cells and is associated with an increased risk of hematologic malignancies and inflammatory disorders ( Jasra et al, 2022 ). Exposure of mice to WTC dust via oropharyngeal aspiration induced mutations in hematopoietic stem cells and progenitor cell compartments ( Jasra et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…Relative to non-WTC-exposed firefighters, DNA sequence analysis of blood from WTC first responders showed increased clonal hematopoiesis, which is the acquisition of somatic mutations in blood cells and is associated with an increased risk of hematologic malignancies and inflammatory disorders ( Jasra et al, 2022 ). Exposure of mice to WTC dust via oropharyngeal aspiration induced mutations in hematopoietic stem cells and progenitor cell compartments ( Jasra et al, 2022 ). The small organic fraction of WTC dust may be a possible cause of these mutations; however, metals and chronic inflammation from the large inorganic fraction could also play a role.…”

Section: Discussionmentioning

confidence: 99%

Mutagenicity of the organic fraction of World Trade Center dust

DeMarini

Warren

Brooks

2022

Environ and Mol Mutagen

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Most studies of the health effects and chemical characterization of the dust resulting from the catastrophic collapse of the World Trade Center (WTC) on September 11, 2001, have focused on the large inorganic fraction of the dust; however, chemical analyses have identified mutagens and carcinogens in the smaller organic fraction. Here, we determined the mutagenicity of the organic fraction of WTC dust in Salmonella. Only 0.74% of the mass of the particulate matter (PM) <53 μm in diameter was extractable organic matter (EOM). Because the EOM was 10 times more mutagenic in TA100 +S9 than in TA98 +S9 and was negative in TA98 −S9, we inferred, respectively, that polycyclic aromatic hydrocarbons (PAHs) played a role in the mutagenicity and not nitroarenes. In TA98 +S9, the mutagenic potency of the EOM (0.1 revertant/μg EOM) was within the range of EOMs from air and combustion emissions. However, the EOM‐based mutagenic potency of the particles (0.0007 revertants/μg PM) was 1–2 orders of magnitude lower than values from a review of 50 combustion emissions and various air samples. We calculated that 37 PAHs analyzed previously in WTC EOM were 5.4% of the EOM mass and 0.04% of the PM mass; some air contained 0.3 μg WTC EOM/m3 (0.02 μg PAHs/m3). Populations exposed to WTC dust have elevated levels of prostate and thyroid cancer but not lung cancer. Our data support earlier estimates that PAH‐associated cancer risk among this population, for example, PAH‐associated lung cancer, was unlikely to be significantly elevated relative to background PAH exposures.

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“…The terrorist attack on the World Trade Center (WTC) in 1993 generated a unique environmental exposure to aerosolized dust, gases, and potential carcinogens in a small population of individuals; it represented a peculiar opportunity to explore the effect of potential environmental carcinogens in clonal hematopoiesis development. 166 Deep targeted sequencing of blood samples showed a significantly higher proportion of individuals with CHIP among WTC-exposed first responders compared to non-WTC-exposed firefighters after controlling for age, sex, and race/ethnicity (10% vs. 6.7%, respectively). 166 CHIP mutations predominantly affected TET2 and DNMT3A .…”

Section: Clonal Hematopoiesis In Cancermentioning

confidence: 95%

“… 166 Deep targeted sequencing of blood samples showed a significantly higher proportion of individuals with CHIP among WTC-exposed first responders compared to non-WTC-exposed firefighters after controlling for age, sex, and race/ethnicity (10% vs. 6.7%, respectively). 166 CHIP mutations predominantly affected TET2 and DNMT3A . 166 …”

Section: Clonal Hematopoiesis In Cancermentioning

confidence: 95%

Clonal Hematopoiesis: Role in Hematologic Non-Hematologic

Testa¹,

Castelli²

2022

Mediterr J Hematol Infect Dis

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Hematopoietic stem cells (HSCs) ensure the coordinated and balanced production of all hematopoietic cell types throughout life. Aging is associated with a gradual decline of the self-renewal and regenerative potential of HSCs and with the development of clonal hematopoiesis. Clonal hematopoiesis of indeterminate potential (CHIP) is a term defining the clonal expansion of genetically variant hematopoietic cells bearing one or more gene mutations and/or structural variants (such as copy number alterations). CHIP increases exponentially with age and is associated with cancers, including hematologic neoplasia, cardiovascular and other diseases. The presence of CHIP consistently increases the risk of hematologic malignancy, particularly in individuals who have CHIP in association with peripheral blood cytopenia. Key words: hematopoiesis, hematopoietic stem cells, clonal hematopoiesis, gene mutations, next generation sequencing.

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

Cited by 27 publications

References 20 publications

Characteristics of Women with Lung Adenocarcinoma in the World Trade Center Environmental Health Center

Characteristics of Women with Lung Adenocarcinoma in the World Trade Center Environmental Health Center

Mutagenicity of the organic fraction of World Trade Center dust

Clonal Hematopoiesis: Role in Hematologic Non-Hematologic

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