The pathogenesis of mesothelioma

Our plain-English summary of The pathogenesis of mesothelioma, by M. Carbone, R.A. Kratzke, J.R. Testa (Seminars in Oncology, 2002).

The study

• Authors: M. Carbone, R.A. Kratzke, J.R. Testa
• Journal: Seminars in Oncology
• Published: 2002;29(1):2-17
• Type of article: Review
• Cited by: 285 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

About 80% of malignant mesotheliomas (MM) in the Western World develop in individuals with higher than background exposure to asbestos. Only a fraction of those exposed to asbestos develop mesothelioma, indicating that additional factors play a role. Simian virus 40 (SV40), a DNA tumor virus that preferentially causes mesothelioma in hamsters, has been detected in several human mesotheliomas. The expression of the SV40 large tumor antigen in mesothelioma cells, and not in nearby stromal cells, and the capacity of antisense T-antigen treatment to arrest mesothelioma cell growth in vitro suggest that SV40 contributes to tumor development. The capacity of T-antigen to bind and inhibit cellular p53 and retinoblastoma (Rb)-family proteins in mesothelioma, together with the very high susceptibility of human mesothelial cells to SV40-mediated transformation in vitro, supports a causative role of SV40 in the pathogenesis of mesothelioma. Asbestos appears to increase SV40-mediated transformation of human mesothelial cells in vitro, suggesting that asbestos and SV40 may be cocarcinogens. p53 mutations are rarely found in mesothelioma; p16, p14ARF, and NF2 mutations/losses are frequent. Recent studies revealed the existence of a genetic factor that predisposes affected individuals to mesothelioma in the villages of Karain and Tuzkoy, in Anatolia, Turkey. Erionite, a type of zeolite, may be a cofactor in these same villages, where 50% of deaths are caused by mesothelioma. Mesothelioma appears to have a complex etiology in which environmental carcinogens (asbestos and erionite), ionizing radiation, viruses, and genetic factors act alone or in concert to cause malignancy.

Copyright 2002 by W.B. Saunders Company.

In plain English

This article was a narrative review, not a new study. The authors summarized published research on how malignant mesothelioma develops. It covered asbestos, simian virus 40 (SV40), radiation, inherited susceptibility and the mineral erionite, drawing on human, animal and cell-culture studies. They wrote that about 80% of malignant mesotheliomas in the Western World develop in people with higher than background exposure to asbestos, and that about 5% of asbestos workers develop the disease. Citing a South African mining study, they reported mesothelioma in 4.7% of deaths among crocidolite miners and 0.6% of deaths among amosite miners. They judged crocidolite more carcinogenic than chrysotile. Their reading of lung fiber studies suggested mesothelioma was not directly related to the amount of exposure. They described earlier work finding SV40 in 29 of 48 mesothelioma samples. They also described family studies in Karain and Tuzkoy, Turkey, where about half the descendants of affected parents developed mesothelioma. They noted that exposure histories are imprecise. The authors concluded that genetics, radiation, viruses and environmental carcinogens such as asbestos and erionite may interact to cause mesothelioma.

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 (no new data collected by the authors)
• Who was studied: Published literature on human mesothelioma (patients, asbestos miners, families, villagers of Karain and Tuzkoy in Cappadocia, Turkey), animal experiments (rats, hamsters) and cell-culture studies
• Exposure: Asbestos (chrysotile, and the amphiboles crocidolite, amosite, anthophyllite and tremolite), SV40 virus (linked to contaminated polio vaccines), radiation, erionite, and genetic factors
• Main results:
  • The authors stated that about 80% of malignant mesotheliomas in the Western World develop in individuals with higher than background exposure to asbestos
  • The authors stated, citing other work, that about 5% of asbestos workers develop mesothelioma
  • In a cited South African mortality study of 1,225 deaths among 7,317 crocidolite or amosite miners, 30 deaths were mesotheliomas: 20 in crocidolite miners (of 423 deaths, 4.7%), 4 in amosite miners (of 648 deaths, 0.6%), and 6 in miners with mixed exposure (of 154 deaths, 3.9%)
  • The authors judged crocidolite asbestos more carcinogenic than chrysotile
  • A cited review of 21 reports covering 1,690 mesotheliomas found none occurring less than 10 years after asbestos exposure, with a mean latency of 32 years
  • From published lung fiber content studies, the authors observed that mesothelioma did not appear directly related to the amount of exposure. Mesothelioma occurred with exposures above background but considerably lower than those seen in asbestosis patients
  • A cited earlier study found SV40 sequences in 29 of 48 (60%) human mesothelioma samples
  • In family pedigrees from Karain and Tuzkoy, Turkey, about 50% of descendants of affected parents developed mesothelioma, while other families had none. Mineralogical analyses (reported as a personal communication) found no difference in erionite between affected and other houses
  • Among acquired genetic changes, p53 is rarely mutated in mesothelioma, while NF2 mutations have been reported in 40% to 55% of mesothelioma cell lines
  • The authors considered radiation a cause of only a small number of mesotheliomas
• The authors' conclusion: The authors concluded that mesothelioma may be a cancer in which genetics, radiation, viruses and environmental carcinogens such as asbestos and erionite interact to cause malignancy
• Limitations the authors state:
  • The authors noted that studies estimating asbestos exposure from patients' histories are inherently imprecise
  • The authors noted that lung content analyses are also limited, because asbestos levels vary within the same lung

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Background Exposure, SV40, Mesothelial Cells, Karain, erionite, Zeolite.

Related studies

• Pathogenesis of malignant pleural mesothelioma — M.C. Jaurand, J. Fleury-Feith (2005)
• SV40-induced expression of calretinin protects mesothelial cells from asbestos cytotoxicity and may be a key factor contributing to mesothelioma pathogenesis — T. Henzi, W.V. Blum, et al. (2009)
• Mesothelioma not associated with asbestos exposure — B. Jasani, A. Gibbs (2012)
• Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection — M. Suzuki, S. Toyooka, et al. (2005)
• SV40 and the pathogenesis of mesothelioma — P. Rizzo, M. Bocchetta, et al. (2001)
• Molecular pathogenesis of malignant mesothelioma and its relationship to simian virus 40 — A.F. Gazdar, M. Carbone (2003)

Browse more research in Seminars in Oncology, or return to medical research.