Molecular pathogenesis of malignant mesothelioma and its relationship to simian virus 40

Our plain-English summary of Molecular pathogenesis of malignant mesothelioma and its relationship to simian virus 40, by A.F. Gazdar, M. Carbone (Clinical Lung Cancer, 2003).

The study

• Authors: A.F. Gazdar, M. Carbone
• Journal: Clinical Lung Cancer
• Published: 2003;5(3):177-81
• Type of article: Review
• Cited by: 45 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma is a relatively rare tumor, but the incidence of the disease appears to be increasing. Unique molecular changes are associated with the disease that distinguish it from lung cancers. Smoking is not an etiologic factor; the major causative agent is asbestos exposure, usually many years or decades before the development of the tumor. Recently, a simian virus, SV40, has been associated with malignant mesotheliomas and is a probable cofactor in tumor development. The molecular changes caused by each of these major etiologic factors and their interrelationships are the focus of this review.

In plain English

This article was a review of published research on how malignant mesothelioma develops at the molecular level, not a new study. The authors focused on asbestos, which they called the major cause, and simian virus 40 (SV40), a monkey virus they described as associated with mesothelioma and a probable cofactor. Millions of Americans, they noted, received SV40 through contaminated polio vaccine from 1955 to 1963 and possibly afterward. The authors stated that about 80% of U.S. cases are associated with asbestos exposure, and that only about 5% of asbestos-exposed persons develop the disease. They described amphiboles, represented by crocidolite, as more carcinogenic than serpentine fibers such as chrysotile, and stated that mesothelioma is not associated with smoking. They also reviewed reported gene changes, such as loss of the p16INK4a gene product. On SV40, they noted more than 30 positive reports and rare negative ones, and acknowledged considerable skepticism in the scientific community about the data. The authors concluded that neither asbestos nor SV40 appears sufficient or necessary on its own, that both may contribute, and that their combined effects may be greater than simply additive.

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 on the molecular causes of malignant mesothelioma, with some mention of the authors' own earlier and unpublished findings
• Who was studied: No study population; the authors reviewed published laboratory, genetic and epidemiologic research on malignant mesothelioma
• Exposure: Asbestos (serpentine fibers represented by chrysotile; amphiboles represented by crocidolite) and simian virus 40 (SV40), which the authors described as reaching people through contaminated polio vaccine during 1955 to 1963 and possibly afterward; the nonasbestos fiber erionite was also discussed
• Main results:
  • The authors described SV40 as associated with malignant mesothelioma and as a probable cofactor in tumor development, not as an established cause
  • The authors stated that in the United States about 80% of mesothelioma cases are associated with asbestos exposure
  • The authors stated that only a small proportion of asbestos-exposed persons, about 5%, develop mesothelioma
  • The authors described amphibole fibers as more carcinogenic than serpentine fibers. They called crocidolite the most oncogenic form and chrysotile the most common fiber in North America.
  • The authors stated that, unlike lung cancer after asbestos exposure, mesothelioma is not associated with smoking
  • Citing other research, the authors reported that mesothelioma cell lines and tumors lacked the p16INK4a gene product in all cases
  • The authors reported more than 30 positive reports linking SV40 to mesothelioma, as well as rare negative reports
  • In a laboratory (in vitro) model of human mesothelial cells transformed by SV40, which the authors cited, asbestos acted as a cocarcinogen
• The authors' conclusion: The authors concluded that asbestos is the major cause of mesothelioma, but that neither asbestos nor SV40 appears sufficient or necessary on its own. They concluded that both may contribute, possibly with combined effects greater than simply additive.
• Limitations the authors state:
  • The authors acknowledged considerable skepticism in the scientific community about whether the SV40 findings are accurate and what they mean
  • The authors noted that U.S. incidence figures are estimates, because national sampling data may not be representative for mesothelioma
  • The authors noted that their own finding of low methylation in mesothelioma may have been influenced by which genes were selected for testing

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Lung Cancer, Asbestos Exposure, SV40.

Related studies

• The relationship between simian virus 40 and mesothelioma — Z. Rivera, O. Strianese, et al. (2008)
• No implication of Simian virus 40 in pathogenesis of malignant pleural mesothelioma in Slovenia — J. Hmeljak, I. Kern, et al. (2010)
• Mesothelioma mortality in Europe: impact of asbestos consumption and simian virus 40 — K. Leithner, A. Leithner, et al. (2006)
• Simian virus 40 is present in most United States human mesotheliomas, but it is rarely present in non-Hodgkin's lymphoma — P. Rizzo, M. Carbone, et al. (1999)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• Simian virus 40 transformation, malignant mesothelioma and brain tumors — F. Qi, M. Carbone, et al. (2011)

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