Molecular and genetic changes in asbestos-related lung cancer

Our plain-English summary of Molecular and genetic changes in asbestos-related lung cancer, by P. Nymark, H. Wikman, T. Hienonen-Kempas, et al (Cancer Letters, 2008).

The study

• Authors: P. Nymark, H. Wikman, T. Hienonen-Kempas, S. Anttila
• Journal: Cancer Letters
• Published: 2008;265(1):1-15
• Type of article: Review
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos-exposure is associated with an increased risk of lung cancer, one of the leading causes of cancer deaths worldwide. Asbestos is known to induce DNA and chromosomal damage as well as aberrations in signalling pathways, such as the MAPK and NF-kappaB cascades, crucial for cellular homeostasis. The alterations result from both indirect effects through e.g. reactive oxygen/nitrogen species and direct mechanical disturbances of cellular constituents. This review describes the current knowledge on genomic and pathway aberrations characterizing asbestos-related lung cancer. Specific asbestos-associated molecular signatures can assist the development of early biomarkers, molecular diagnosis, and molecular targeted treatments for asbestos-exposed lung cancer patients.

In plain English

This article was a mini-review that reported no new data of its own. It reviewed published cell, animal and human studies on the molecular and genetic changes in asbestos-related lung cancer. The review described how asbestos fibres can damage DNA and chromosomes and disturb cell signalling pathways. Among the human findings, two studies, one of them the authors' own earlier work, found loss of chromosome region 3p more often in tumours of asbestos-exposed than non-exposed patients. A link between asbestos exposure and TP53 mutations in lung cancer patients was found in many studies, but not in all. A pooled study of 651 lung cancer cases and 983 controls found no relation between asbestos exposure and the GSTM1 or GSTT1 null genotypes. The authors noted that most asbestos-exposed lung cancer patients also smoke, making asbestos-related changes very hard to separate from tobacco-related ones. The authors concluded that asbestos-specific molecular changes could enable molecular diagnosis and the identification of treatment targets. They also judged it probable that a reliable diagnostic test would combine several asbestos-associated changes, both more and less specific to asbestos.

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 (mini-review) of published experimental and human studies
• Who was studied: Published in vitro (cell line), animal, and human lung cancer studies; no single study population of the authors' own
• Exposure: Asbestos in general (the review lists chrysotile, crocidolite, amosite, tremolite, anthophyllite and actinolite), often in combination with tobacco smoke
• Main results:
  • The review reported that two studies, including the authors' own earlier work, found loss of chromosome region 3p more frequently in tumours of asbestos-exposed than of non-exposed lung cancer patients
  • The review described a study (Suzuki et al.) of five tumorigenic human bronchial epithelial cell lines transformed by chrysotile asbestos. The common changes were loss of one or two copies of chromosome 5, loss of one copy of chromosome 19, and an extra copy of chromosome 8
  • The review reported that TP53 mutations were positively associated with asbestos exposure in lung cancer patients in many, but not all, studies
  • The review cited a study of 355 cases in which mutations in codon 12 of the KRAS gene were significantly associated with asbestos-related lung adenocarcinoma. An earlier association could not be confirmed when cases were added to that earlier study
  • The review cited a pooled study of 651 lung cancer cases and 983 controls that found no relation between asbestos exposure and the GSTM1 or GSTT1 null genotypes
  • The review cited a case-control study (Schabath et al.) of 375 Caucasian lung cancer cases and 378 matched controls. At a similar level of asbestos exposure, people with the MPO A-allele genotypes (G/A and A/A) had a reduced risk of lung cancer
• The authors' conclusion: The authors concluded that asbestos-specific molecular changes in cancer could enable molecular diagnosis and the identification of therapeutic targets. They judged it probable that a reliable diagnostic test would combine several different asbestos-associated molecular changes, since both the more and the less asbestos-specific changes may contribute to the carcinogenic effects of asbestos.
• Limitations the authors state:
  • Most asbestos-exposed lung cancer patients are also smokers, which makes it very difficult to tell asbestos-related molecular changes apart from tobacco-related ones
  • Most studies of chromosomal changes in human lung tumours did not report the patients' asbestos exposure
  • Changes linked to oxidative stress are less specific to asbestos, because many other genotoxins also cause oxidative stress
  • Suitable animal models (and in vitro models) of asbestos lung carcinogenesis have been difficult to establish

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Biomarker.

Related studies

• Identification of specific gene copy number changes in asbestos-related lung cancer — P. Nymark, H. Wikman, et al. (2006)
• Molecular changes in mesothelioma with an impact on prognosis and treatment — D. Jean, J. Daubriac, et al. (2012)
• Malignant pleural mesothelioma: newer aspects of carcinogenesis, molecular genetics, and prospects for future therapies — J.S. Donington, D.J. Mew, et al. (1995)
• Cytogenetic and molecular genetic changes in malignant mesothelioma — M. Musti, E. Kettunen, et al. (2006)
• Genetic susceptibility to asbestos-related fibrotic pleuropulmonary changes — M.K. Kukkonen, S. Hämäläinen, et al. (2011)
• Molecular alterations at 9q33.1 and polyploidy in asbestos-related lung cancer — P. Nymark, E. Kettunen, et al. (2009)

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