Pathogenesis of malignant mesothelioma

Our plain-English summary of Pathogenesis of malignant mesothelioma, by M. Carbone, M.A. Rdzanek (Clinical Lung Cancer, 2004).

The study

• Authors: M. Carbone, M.A. Rdzanek
• Journal: Clinical Lung Cancer
• Published: 2004;5 Suppl 2:S46-50
• Type of article: Review
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is a very aggressive tumor that is caused by environmental, biologic, and genetic factors. Among these factors, asbestos plays a major role. The link between asbestos and MM has been firmly established through numerous epidemiologic studies conducted during the past 40 years. However, the causal role of chrysotile asbestos compared with crocidolite asbestos in MM, the method of correctly establishing asbestos exposure, the amount of asbestos necessary to cause MM, and the mechanisms of asbestos tumorigenicity are still being debated. Along with asbestos, Simian virus 40 (SV40), a DNA monkey virus, has recently been implicated in the etiology of MM. Simian virus 40 large T antigen (Tag) and small t antigen (tag) are largely responsible for the carcinogenicity of the virus, and it is possible that SV40 and asbestos are cocarcinogens. Finally, a genetic factor identified in 3 villages in Cappadocia, Turkey, where 50% of individuals die of MM, appears to be the cause of a high incidence of the disease. In these villages, genetic predisposition for MM works together with erionite, a nonasbestos fiber found in the stones used in construction of houses. The diagnosis of MM is made histologically and confirmed through electron microscopy and immunohistochemistry. Currently available therapies for MM prolong survival by a few months at most. An SV40 vaccine is being developed for human use and it is hoped that it may reduce the incidence of MM in asbestos workers.

In plain English

This article was a narrative review, not a new study, of what was known about how malignant mesothelioma arises. The authors summarized other researchers' work on asbestos, Simian virus 40 (SV40, a monkey virus), genetics, erionite and radiation. They wrote that about 80% of United States mesothelioma patients had been exposed to asbestos, but only 5% of those professionally exposed develop the disease. They said the role of amphiboles was well accepted, while the link between chrysotile and mesothelioma was still controversial. A cited review of 1690 cases found a mean latency of 32 years. The authors preferred lung content analysis over patient interviews for establishing exposure. They reported that about 50% of mesothelioma cases contain SV40. They also described a cited laboratory study in which human mesothelial cells became malignant only when a mutant SV40 was combined with asbestos. Describing their own family-tree work on 6 families in Turkish villages, they said the results suggested an inherited susceptibility. The authors concluded that mesothelioma is caused by environmental, biologic and genetic factors working alone or together.

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 causes and mechanisms of malignant mesothelioma, with a brief description of the authors' own earlier pedigree (family tree) work in Turkey
• Who was studied: No new study population. The article reviewed published human, animal and cell studies. It also described pedigrees of 6 families with frequent mesothelioma in villages in Cappadocia, Turkey.
• Exposure: Asbestos: chrysotile and the amphiboles (crocidolite, amosite, anthophyllite, actinolite). Also Simian virus 40 from contaminated polio vaccines, erionite (a nonasbestos fiber in building stones), radiation, and household (second-hand) asbestos exposure.
• Main results:
  • The review stated that about 80% of patients with mesothelioma in the United States have been exposed to asbestos, but only 5% of those professionally exposed to asbestos develop mesothelioma.
  • The review stated that the role of amphiboles in mesothelioma is well accepted, while the link between chrysotile and mesothelioma is still controversial.
  • A cited hamster experiment: 4% of hamsters injected with 1 mg of asbestos and 20% of those injected with 10 mg developed tumors.
  • A cited review of 1690 mesothelioma cases found a mean latency period of 32 years.
  • The authors judged lung content analysis better than patient interviews for establishing asbestos exposure. Among their reasons were patients' imperfect recall and, in their view, an incentive to exaggerate exposure because of court compensation.
  • Worldwide, mesothelioma incidence in women was reported as 2 to 10 times lower than in men. A cited study of 6 cases linked household asbestos exposure to mesothelioma. In 5 of those cases the exposure came from hand-laundering a spouse's work clothes.
  • The review reported that about 50% of human mesothelioma cases contain SV40. A cited study found SV40 sequences not detectable in 49 of 49 Finnish mesothelioma patients.
  • In a cited laboratory study, asbestos alone did not malignantly transform human mesothelial cells, and neither did mutant SV40 alone. Cells given mutant SV40 and then exposed to asbestos were transformed, which the authors described as a cocarcinogenic effect.
  • In the Turkish villages of Karain and Tuzkoy, 50% of deaths were reported to be from mesothelioma. A neighboring village built with the same erionite-containing stones had only one case. The authors' pedigrees of 6 families suggested an autosomal dominant inherited susceptibility.
  • The review described a few cases of mesothelioma after radiation, with latency of 7 to 36 years, and called radiation-caused mesothelioma very rare.
• The authors' conclusion: The authors concluded that malignant mesothelioma is caused by environmental, biologic and genetic factors that work alone or together. They also concluded that SV40 offers a possible target for prevention or treatment.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Chrysotile, Crocidolite, Asbestos Exposure, SV40, Etiology, Cappadocia, erionite.

Related studies

• The pathogenesis of mesothelioma — M. Carbone, R.A. Kratzke, et al. (2002)
• 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)
• 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)
• Prospects for an SV40 vaccine — M.J. Imperiale, H.I. Pass, et al. (2001)

Browse more research in Clinical Lung Cancer, or return to medical research.