World Trade Center Exposure, DNA Methylation Changes, and Cancer: A Review of Current Evidence

Our plain-English summary of World Trade Center Exposure, DNA Methylation Changes, and Cancer: A Review of Current Evidence, by S. Tuminello, E. Nguyen, N. Durmus, et al (Epigenomes, 2023).

The study

• Authors: S. Tuminello, E. Nguyen, N. Durmus, R. Alptekin, M. Yilmaz, M.C. Crisanti, M. Snuderl, Y. Chen, Y. Shao, J. Reibman, E. Taioli, A.A. Arslan
• Journal: Epigenomes
• Published: 2023;7(4)
• Type of article: Review
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Known carcinogens in the dust and fumes from the destruction of the World Trade Center (WTC) towers on 9 November 2001 included metals, asbestos, and organic pollutants, which have been shown to modify epigenetic status. Epigenome-wide association analyses (EWAS) using uniform (Illumina) methodology have identified novel epigenetic profiles of WTC exposure. Methods: We reviewed all published data, comparing differentially methylated gene profiles identified in the prior EWAS studies of WTC exposure. This included DNA methylation changes in blood-derived DNA from cases of cancer-free "Survivors" and those with breast cancer, as well as tissue-derived DNA from "Responders" with prostate cancer. Emerging molecular pathways related to the observed DNA methylation changes in WTC-exposed groups were explored and summarized. Results: WTC dust exposure appears to be associated with DNA methylation changes across the genome. Notably, WTC dust exposure appears to be associated with increased global DNA methylation; direct dysregulation of cancer genes and pathways, including inflammation and immune system dysregulation; and endocrine system disruption, as well as disruption of cholesterol homeostasis and lipid metabolism. Conclusion: WTC dust exposure appears to be associated with biologically meaningful DNA methylation changes, with implications for carcinogenesis and development of other chronic diseases.

In plain English

This was a review, not a new study. The authors compared the four published studies that had measured DNA methylation (chemical marks on DNA that can affect gene activity) across the genome in people exposed to dust from the World Trade Center collapse in 2001. The authors note the dust contained metals, asbestos and organic pollutants. The review did not report results for asbestos on its own. Three studies, by members of this author group, compared exposed and unexposed people: blood from 18 cancer-free exposed women (community "Survivors"), blood from 28 exposed women with breast cancer, and prostate tumor tissue from exposed rescue and recovery "Responders." A fourth compared male Responders with high and low exposure. The authors reported that all three studies with unexposed groups found higher overall methylation in exposed people. Across the studies, they also reported changes in genes and pathways tied to cancer, immunity and inflammation, hormones, and cholesterol and fat metabolism. They concluded that the studies revealed a potential relationship between exposure and these changes and that larger studies are needed. They noted that there were few studies and that the studies differed in sex, sample type and data processing.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of previously published epigenome-wide association studies (EWAS) of World Trade Center (WTC) exposure and DNA methylation, with a comparison of common biological themes across three of them
• Who was studied: Four published EWAS studies of WTC-exposed people. Kuan et al., 2019: blood from 185 male Responders, 116 with a high WTC exposure ranking index and 69 with a low one. Arslan et al., 2020: blood from 18 WTC-exposed cancer-free female Survivors vs 24 unexposed cancer-free females. Tuminello et al., 2022: blood from 28 WTC-exposed female Survivors with breast cancer vs 24 unexposed females with pre-diagnostic breast cancer. Yu et al., 2022: prostate tumor tissue from WTC-exposed male Responders vs unexposed males with prostate cancer. The article gives 12 vs 13 in its methods and 13 vs 15 in Table 1. Only the three studies with unexposed control groups were used for the theme comparison.
• Exposure: Dust and fumes from the destruction of the World Trade Center towers. The authors describe the dust as containing carcinogens such as metals, asbestos and organic pollutants. No fiber type is named, and no results are given for asbestos separately.
• Main results:
  • All three studies with an unexposed control group (cancer-free Survivors, Survivors with breast cancer, Responders with prostate cancer) independently observed increased global DNA methylation associated with WTC exposure.
  • In both cancer studies (Survivors with breast cancer and Responders with prostate cancer), increased DNA methylation was observed for the BRCA1, NOTCH1, PALB2 and WRN tumor suppressor genes. Dysregulation of the oncogenes KRAS and NTRK1 was also reported.
  • Immune-related pathways were enriched in the cancer-free Survivor, breast cancer and prostate cancer studies.
  • Endocrine pathways were enriched in the breast cancer study (for example thyroid hormone signaling) and the prostate cancer study (androgen response). The authors described this evidence as preliminary.
  • Pathways related to cholesterol and lipid metabolism were enriched in the cancer-free Survivor and breast cancer Survivor studies.
  • The Kuan et al., 2019 study of male Responders with high vs low exposure did not find any statistically significant DNA methylation sites after adjustment for multiple testing.
• The authors' conclusion: The authors concluded that the previously published studies revealed a potential relationship between WTC exposure and epigenetic dysregulation, with relevance for cancer risk, and that additional studies are needed.
• Limitations the authors state:
  • Only a small number of EWAS studies have been published.
  • EWAS studies are prone to several biases, including technical variation, cell type differences and unmeasured confounding.
  • The individual studies had limited generalizability because of selection bias.
  • In the breast cancer study, blood from unexposed women came from cases taken before breast cancer was diagnosed.
  • The studies differed in participant sex and sample type (blood or tissue).
  • Data processing steps, such as normalization and adjustment for cell types, differed between the studies.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Carcinogenesis.

Related studies

• Mesothelioma Cases in the World Trade Center Survivors — M.E. Yilmaz, M. Rashidfarokhi, et al. (2024)
• Characterization of the dust/smoke aerosol that settled east of the World Trade Center (WTC) in lower Manhattan after the collapse of the WTC 11 September 2001 — P.J. Lioy, C.P. Weisel, et al. (2002)
• Health and environmental consequences of the world trade center disaster — P.J. Landrigan, P.J. Lioy, et al. (2004)
• Acute eosinophilic pneumonia in a New York City firefighter exposed to World Trade Center dust — W.N. Rom, M. Weiden, et al. (2002)
• Health effects of World Trade Center (WTC) Dust: An unprecedented disaster's inadequate risk management — M. Lippmann, M.D. Cohen, et al. (2015)
• Case report: Lung disease in World Trade Center responders exposed to dust and smoke: carbon nanotubes found in the lungs of World Trade Center patients and dust samples — M. Wu, R.E. Gordon, et al. (2010)

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