The Evolving Landscape of the Molecular Epidemiology of Malignant Pleural Mesothelioma

Our plain-English summary of The Evolving Landscape of the Molecular Epidemiology of Malignant Pleural Mesothelioma, by S. Lettieri, C. Bortolotto, F. Agustoni, et al (Journal of Clinical Medicine, 2021).

The study

• Authors: S. Lettieri, C. Bortolotto, F. Agustoni, F. Lococo, A. Lancia, P. Comoli, A.G. Corsico, G.M. Stella
• Journal: Journal of Clinical Medicine
• Published: 2021;10(5)
• Type of article: Review
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural lining of the lungs. It has a strong association with exposure to biopersistent fibers, mainly asbestos (80% of cases) and-in specific geographic regions-erionite, zeolites, ophiolites, and fluoro-edenite. Individuals with a chronic exposure to asbestos generally have a long latency with no or few symptoms. Then, when patients do become symptomatic, they present with advanced disease and a worse overall survival (about 13/15 months). The fibers from industrial production not only pose a substantial risk to workers, but also to their relatives and to the surrounding community. Modern targeted therapies that have shown benefit in other human tumors have thus far failed in MPM. Overall, MPM has been listed as orphan disease by the European Union. However, molecular high-throughput profiling is currently unveiling novel biomarkers and actionable targets. We here discuss the natural evolution, mainly focusing on the novel concept of molecular epidemiology. The application of innovative endpoints, quantification of genetic damages, and definition of genetic susceptibility are reviewed, with the ultimate goal to point out new tools for screening of exposed subject and for designing more efficient diagnostic and therapeutic strategies.

In plain English

This article is a review, not a new study. The authors looked at published research on the "molecular epidemiology" of malignant pleural mesothelioma (MPM): the study of genetic and other biological markers of exposure, risk and disease. They described asbestos (chrysotile and the amphiboles crocidolite, amosite and tremolite) as the main cause and also discussed erionite and fluoro-edenite. Citing an earlier study, they reported that about 88% of pleural and 58% of peritoneal mesotheliomas in men could be related to asbestos. Results for women were less conclusive, at 23% of all mesotheliomas. They reviewed inherited mutations, mainly in BAP1, more rarely in CDKN2A, TP53 and NF2. They noted reports of BAP1 loss in about 50% of sporadic mesotheliomas, and that across studies no confirmed driver gene was found to be activated in the tumors. They also covered blood markers such as HMGB1 and microRNAs. The authors concluded that the approach is emerging as a diagnostic, prognostic and therapeutic tool. They added that it is still at an early stage, limited by the disease's rarity, nonspecific symptoms and long latency after asbestos exposure.

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 (no new data collected)
• Who was studied: No study population of its own. The review draws on published research on malignant pleural mesothelioma, including patients, exposed groups, families, cell lines and animal models.
• Exposure: Asbestos, described as serpentine (chrysotile) and amphibole (crocidolite, amosite, tremolite) fibers. Also other minerals such as erionite and fluoro-edenite, and ionizing radiation.
• Main results:
  • Citing an earlier study (not this one), the authors reported that about 88% of pleural and 58% of peritoneal mesotheliomas in men could be related to asbestos exposure. In women the results were less conclusive, with only 23% of all mesotheliomas attributable to asbestos.
  • The review states that in about 20% of MPM cases, asbestos exposure is not reported or cannot be documented.
  • From earlier studies, inherited (germline) BAP1 mutations were first described in two families with high MPM incidence.
  • From earlier studies, BAP1 loss has been reported in about 50% of sporadic mesotheliomas.
  • Inherited mutations in other genes (CDKN2A, TP53, NF2) were reported more rarely in families with clusters of mesothelioma.
  • Across the studies reviewed, no somatic activation in a confirmed driver gene was found in MPM tumors. Recurrent somatic mutations were reported in tumor-suppressor genes such as CDKN2A and NF2.
  • The review cites a study reporting that blood levels of HMGB1 have been validated as a marker for monitoring workers and their families with a history of asbestos exposure.
• The authors' conclusion: The authors concluded that molecular and genetic epidemiology is emerging as a tool for diagnosis, prognosis and treatment of MPM.
• Limitations the authors state:
  • The authors state that applying these techniques to MPM is at an early stage. They say it is limited by the disease's rarity, its nonspecific symptoms and the long latency after asbestos exposure.
  • The authors note that a high share of MPM diagnoses are incorrect, from 14% in developed countries to 50% in the poorest, which hampers epidemiologic study.
  • The authors list limits of biomarker studies, including markers that may be unreliable or whose biological meaning is unclear.

Topics

Medical terms in this study, explained in our Lexicon: Epidemiology, Pleural Mesothelioma, erionite, Zeolite, Ophiolite, fluoro-edenite, Latency, Overall Survival.

Related studies

• Pleural mesothelioma (PMe): The evolving molecular knowledge of a rare and aggressive cancer — M. Rigon, L. Mutti, et al. (2024)
• Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach — D. Lisini, S. Lettieri, et al. (2021)
• Are glutathione S transferases involved in DNA damage signalling? Interactions with DNA damage and repair revealed from molecular epidemiology studies — M. Dusinska, M. Staruchova, et al. (2012)
• The molecular epidemiology of asbestos and tobacco in lung cancer — H.H. Nelson, K.T. Kelsey (2002)
• A molecular epidemiology case control study on pleural malignant mesothelioma — C. Bolognesi, F. Martini, et al. (2005)
• Smoking and the molecular epidemiology of lung cancer — D.C. Christiani (2000)

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