The Current Understanding Of Asbestos-Induced Epigenetic Changes Associated With Lung Cancer

Our plain-English summary of The Current Understanding Of Asbestos-Induced Epigenetic Changes Associated With Lung Cancer, by Y.Y. Cheng, E.M. Rath, A. Linton, et al (Lung Cancer, 2020).

The study

• Authors: Y.Y. Cheng, E.M. Rath, A. Linton, M.L. Yuen, K. Takahashi, K. Lee
• Journal: Lung Cancer
• Published: 2020;11:1-11
• Type of article: Review
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos is a naturally occurring mineral consisting of extremely fine fibres that can become trapped in the lungs after inhalation. Occupational and environmental exposures to asbestos are linked to development of lung cancer and malignant mesothelioma, a cancer of the lining surrounding the lung. This review discusses the factors that are making asbestos-induced lung cancer a continuing problem, including the extensive historic use of asbestos and decades long latency between exposure and disease development. Genomic mutations of DNA nucleotides and gene rearrangements driving lung cancer are well-studied, with biomarkers and targeted therapies already in clinical use for some of these mutations. The genes involved in these mutation biomarkers and targeted therapies are also involved in epigenetic mechanisms and are discussed in this review as it is hoped that identification of epigenetic aberrations in these genes will enable the same gene biomarkers and targeted therapies to be used. Currently, understanding of how asbestos fibres trapped in the lungs leads to epigenetic changes and lung cancer is incomplete. It has been shown that oxidoreduction reactions on fibre surfaces generate reactive oxygen species (ROS) which in turn damage DNA, leading to genetic and epigenetic alterations that reduce the activity of tumour suppressor genes. Epigenetic DNA methylation changes associated with lung cancer are summarised in this review, and some of these changes will be due to asbestos exposure. So far, little research has been carried out to separate the asbestos driven epigenetic changes from those due to non-asbestos causes of lung cancer. Asbestos-associated lung cancers exhibit less methylation variability than lung cancers in general, and in a large proportion of samples variability has been found to be restricted to promoter regions. Epigenetic aberrations in cancer are proving to be promising biomarkers for diagnosing cancers. It is hoped that further understanding of epigenetic changes in lung cancer can result in useful asbestos-associated lung cancer biomarkers to guide treatment. Research is ongoing into the detection of lung cancer epigenetic alterations using non-invasive samples of blood and sputum. These efforts hold the promise of non-invasive cancer diagnosis in the future. Efforts to reverse epigenetic aberrations in lung cancer by epigenetic therapies are ongoing but have not yet yielded success.

© 2020 Cheng et al.

In plain English

This article is a review of published research on epigenetic changes in lung cancer and their possible link to asbestos. One such change is DNA methylation, which helps regulate gene activity. The review did not study new patients. The authors wrote that how asbestos causes these changes is not fully understood. They also wrote that many studies have examined microRNAs linked to asbestos-induced epigenetic changes in mesothelioma, but that such work in asbestos-related lung cancers has been limited. Citing an earlier study, they reported that lung cancers in people with no documented occupational asbestos exposure showed larger methylation variability than those of asbestos-exposed people. That study also found hypomethylation of the gene TPO in asbestos-associated lung tumours. The review also summarised blood and sputum tests under development. It noted that, for asbestos-related lung cancers, no epigenetic therapies have yet been implemented clinically. The authors concluded that several epigenetic markers, including CDKN2A, RASSF1A and MGMT, are potentially useful for identifying asbestos-related lung cancers. They added that further studies are needed to clarify the direct link to asbestos. They noted that little research has separated asbestos-driven changes from those due to other causes.

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: Narrative review of published literature
• Who was studied: No new patients or subjects. The review covered published studies on lung cancer, including asbestos-related lung cancer.
• Exposure: Asbestos in general. The review states that all forms are carcinogenic and cites studies of chrysotile and crocidolite inducing oxidative stress.
• Main results:
  • The authors stated that the way asbestos induces epigenetic changes is not fully understood.
  • The authors noted that many studies have investigated microRNAs associated with asbestos-induced epigenetic alteration in mesothelioma, but there has been only limited exploration in asbestos-related lung cancers.
  • Citing an earlier study (reference 76), the review reports that lung cancer cases with no documented occupational asbestos exposure had larger methylation variability, and a higher proportion of hypomethylated variable sites, than asbestos-exposed subjects.
  • Citing the same earlier study, the review reports that the gene TPO was hypomethylated in asbestos-associated lung tumours.
  • Citing earlier work, the review reports that single-agent epigenetic drugs had limited effect in non-small cell lung cancer. In 103 patients treated between 1972 and 1977, the objective response rate was 8%.
• The authors' conclusion: The authors concluded that six epigenetic biomarkers (CDKN2A, RARB2, RASSF1A, SOX17, TMEFF2 and MGMT) are potentially useful for identifying asbestos-related lung cancers. They added that the direct link between asbestos and these biomarkers still needs to be clarified. They also wrote that, in the context of treating asbestos-related lung cancers, no epigenetic therapies have yet been implemented clinically.
• Limitations the authors state:
  • The authors state that little research has separated asbestos-driven epigenetic changes from changes due to non-asbestos causes of lung cancer.

Topics

Medical terms in this study, explained in our Lexicon: Lung Cancer, Environmental Exposure, Malignant Mesothelioma, Latency, Biomarker, Reactive Oxygen Species (ROS), Asbestos Exposure, Sputum.

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