Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic

Our plain-English summary of Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic, by O.D. Røe, G.M. Stella (European Respiratory Review, 2015).

The study

• Authors: O.D. Røe, G.M. Stella
• Journal: European Respiratory Review
• Published: 2015;24(135):115-31
• Type of article: Historical article, Review
• Cited by: 131 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos is the term for a family of naturally occurring minerals that have been used on a small scale since ancient times. Industrialisation demanded increased mining and refining in the 20th century, and in 1960, Wagner, Sleggs and Marchand from South Africa linked asbestos to mesothelioma, paving the way to the current knowledge of the aetiology, epidemiology and biology of malignant pleural mesothelioma. Pleural mesothelioma is one of the most lethal cancers, with increasing incidence worldwide. This review will give some snapshots of the history of pleural mesothelioma discovery, and the body of epidemiological and biological research, including some of the controversies and unresolved questions. Translational research is currently unravelling novel circulating biomarkers for earlier diagnosis and novel treatment targets. Current breakthrough discoveries of clinically promising noninvasive biomarkers, such as the 13-protein signature, microRNAs and the BAP1 mesothelioma/cancer syndrome, are highlighted. The asbestos history is a lesson to not be repeated, but here we also review recent in vivo and in vitro studies showing that manmade carbon nanofibres could pose a similar danger to human health. This should be taken seriously by regulatory bodies to ensure thorough testing of novel materials before release in the society.

Copyright ©ERS 2015.

In plain English

This article was a narrative review, not a new study, of asbestos history and its link to malignant pleural mesothelioma. They summarized others' work on disease frequency, biology, genetic susceptibility (including the BAP1 gene), blood tests and manmade carbon nanotubes. They reported the World Health Organization and International Agency for Research on Cancer classify all asbestos types as class I carcinogens, with no safe lower threshold identified. They described a meta-analysis of 528 mesothelioma cases and 468 controls from 15 studies; the combined odds ratio for SV40 DNA being present in mesothelioma tumour tissue was 17 (95% CI 10–28). Other studies questioned this, and epidemiological studies found no clear link between SV40 and cancer. In a cited experiment, multi-walled carbon nanotubes were injected into the abdominal cavity of p53 heterozygous mice; mesothelioma developed in five of 20, 17 of 20 and 19 of 20 mice at increasing doses. The authors reported the mesothelin blood test failed for early diagnosis. The authors concluded that pleural mesothelioma is a global, manmade cancer problem with deaths rising from continued asbestos mining and use.

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 research. It also draws on the authors' own earlier gene-expression work and on Norwegian national statistics.
• Who was studied: No new study population. The review covered published human epidemiological, molecular and biomarker studies on malignant pleural mesothelioma, plus animal and cell-culture studies of carbon nanotubes. It also included the authors' earlier analysis of six tumour and seven parietal pleura samples, and Norwegian import and cancer registry data for 1946 to 2010.
• Exposure: Asbestos: the serpentine chrysotile and the amphiboles crocidolite, amosite, tremolite, actinolite and anthophyllite. The review also covered erionite, ionising radiation, simian virus 40 (SV40) from contaminated polio vaccines, and manmade single-walled and multi-walled carbon nanotubes.
• Main results:
  • The review reported that, according to the WHO and IARC, all types of asbestos are classified as class I carcinogens, and asbestos exposure is the major cause of both pleural and peritoneal mesothelioma.
  • The review reported a known dose–response pattern between asbestos exposure and both mesothelioma and lung cancer. It added that, as stated by IARC and WHO, no safe lower threshold has been identified.
  • Citing Italian data on inhabitants never exposed through work at the local factories in Casale Monferrato (Eternit factory) and Broni and Bari (Fibronit factory), the review reported a calculated risk of OR 10.5 and 5.25, respectively, for those living less than 500 m from the factory.
  • Using Norwegian national data, the authors reported that asbestos imports peaked in 1970–1975 and that the apparent mesothelioma peak is now, 40 years later.
  • The review described a meta-analysis of 528 mesothelioma cases and 468 controls from 15 studies. It gave a combined odds ratio for the presence of SV40 DNA sequences in mesothelioma tumour tissue of OR 17, 95% CI 10–28. Other studies suggested such findings were caused by contamination or laboratory artefacts, and epidemiological studies have not shown a clear correlation between SV40 and cancer.
  • The review reported germ-line BAP1 mutations in families with very high mesothelioma incidence and in 25% of sporadic mesotheliomas. It stated that the role of BAP1 in mineral-fibre carcinogenesis has not been established.
  • The review described a 13-protein blood signature identified in a cohort of 117 mesothelioma cases and 142 asbestos-exposed controls.
  • For that 13-protein signature, the diagnostic area under the curve was 0.99 in training, 0.98 in independent blinded verification and 0.95 in blinded validation.
  • The authors stated that the soluble mesothelin (SMRP) blood test failed as an early diagnostic biomarker. They and others had found no significant difference in serum levels between cases and controls before diagnosis.
  • In a cited animal study, multi-walled carbon nanotubes were given by intraperitoneal injection (into the abdominal cavity), not by inhalation, to p53 heterozygous mice, which were followed for 1 year. Mesothelioma developed in five of 20, 17 of 20 and 19 of 20 mice as the dose increased.
  • The authors described their own earlier genome-wide analysis of six mesothelioma tumour and seven parietal pleura samples. It showed dysregulated genes, including genes for DNA replication and repair and genes linked to chemotherapy and radiotherapy resistance.
• The authors' conclusion: The authors concluded that malignant pleural mesothelioma is a global, manmade cancer problem with increasing death tolls due to sustained mining and use of asbestos.
• Limitations the authors state:
  • The authors noted that no prospective studies of asbestos-exposed cohorts had verified the 13-protein signature for early diagnosis and survival.
  • The authors noted that the literature on carbon nanotubes and mesothelioma is scarce.
  • The authors noted the low numbers of cases and controls in their own genome-wide gene-expression analysis.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Epidemiology, Discovery, Biomarker, BAP1.

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• Asbestos-related disease in South Africa: the social production of an invisible epidemic — L. Braun, S. Kisting (2006)
• Role of manmade mineral fibres in the causation of cancer — P.E. Enterline (1990)
• Tumor incidence was not related to the thickness of visceral pleural in female Syrian hamsters intratracheally administered amphibole asbestos or manmade fibers — S. Adachi, K. Kawamura, et al. (1992)
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