Mesothelioma epidemiology, carcinogenesis, and pathogenesis

Our plain-English summary of Mesothelioma epidemiology, carcinogenesis, and pathogenesis, by H. Yang, J.R. Testa, M. Carbone (Current Treatment Options in Oncology, 2008).

The study

• Authors: H. Yang, J.R. Testa, M. Carbone
• Journal: Current Treatment Options in Oncology
• Published: 2008;9(2-3):147-57
• Type of article: Review
• Cited by: 201 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The incidence of mesothelioma has gone from almost none to the current 2500-3000 cases per year in the USA. This estimate is an extrapolation based on information available from the Surveillance, Epidemiology and End Results (SEER) Program that collects information on approximately 12% of the US population. Mesothelioma is a cancer that is linked to exposure to carcinogenic mineral fibers. Asbestos and erionite have a proven causative role; the possible role of other mineral fibers in causing mesothelioma is being investigated. Asbestos is considered the main cause of mesothelioma in the US and in the Western world. The capacity of asbestos to induce mesothelioma has been linked to its ability to cause the release of TNF-alpha (that promotes mesothelial cells survival), other cytokines and growth factors, and of mutagenic oxygen radicals from exposed mesothelial cells and nearby macrophages. Some investigators proposed that as a consequence of the regulations to prevent exposure and to forbid and/or limit the use of asbestos, the incidence of mesothelioma in the US (and in some European countries) should have started to decline before or around the year 2000, and sharply decline thereafter. Unfortunately, there are no data available yet to support this optimistic hypothesis. Simian virus 40 (SV40) infection and radiation exposure are additional causes, although their contribution to the overall incidence of mesothelioma is unknown. Recent data from several laboratories indicate that asbestos exposure and SV40 infection are co-carcinogens in causing mesothelioma in rodents and in causing malignant transformation of human mesothelial cells in tissue culture. An exciting new development comes from the discovery that genetic susceptibility to mineral fiber carcinogenesis plays a critical role in the incidence of this cancer in certain families. It is hoped that the identification of this putative mesothelioma gene will lead to novel mechanistically driven preventive and therapeutic approaches.

In plain English

This article is a review and opinion piece, not an original study; the authors summarized published research on the causes and biology of malignant mesothelioma. They reported about 2000 to 3000 cases per year in the United States and stated that asbestos and erionite have a proven causative role. They cited an estimate that exposure-specific mesothelioma risk is broadly in the ratio 1:100:500 for chrysotile, amosite and crocidolite. They also said an earlier literature review by some of them found the data too contradictory to conclude whether chrysotile does or does not cause mesothelioma. They described laboratory work in which asbestos triggered release of TNF-alpha, which helped exposed mesothelial cells survive. They also described a hamster experiment in which asbestos plus a form of SV40 virus caused mesothelioma in 90% of animals, versus 20% with asbestos alone. They described family studies in Cappadocia, Turkey, pointing to erionite exposure in genetically predisposed people. The authors concluded that mesothelioma is caused by multiple factors that may work alone or in combination.

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 with an opinion statement; no original data were collected
• Who was studied: No study population; the article reviews published research on malignant mesothelioma
• Exposure: Asbestos (chrysotile, and the amphiboles crocidolite, amosite, anthophyllite, actinolite and tremolite), erionite, Simian virus 40 (SV40), genetic predisposition and radiation, as reviewed causes or cofactors of mesothelioma
• Main results:
  • The authors reported about 2000 to 3000 mesothelioma cases per year in the United States, citing another source.
  • The authors described asbestos and erionite as having a proven causative role.
  • The review cited Hodgson and Darnton's estimate that exposure-specific mesothelioma risk is broadly in the ratio 1:100:500 for chrysotile, amosite and crocidolite.
  • The authors stated that an earlier literature review by some of them found the chrysotile data so contradictory that no conclusion could be reached on whether chrysotile causes mesothelioma.
  • The review cited Epidemiological studies finding that about 5% of individuals with heavy prolonged asbestos exposure develop mesothelioma.
  • Cited laboratory work found that TNF-alpha, released in response to asbestos, activates the NF-kappaB pathway and increases the percentage of human mesothelial cells that survive asbestos exposure.
  • In a cited hamster study, asbestos plus SV40 dl883 together caused mesothelioma in 90% of hamsters. SV40 dl883 alone caused none, and asbestos alone caused mesothelioma in 20% of hamsters.
  • In cited rat experiments, injected erionite caused pleural mesothelioma in 40 of 40 rats, compared with 19 of 40 rats injected with asbestos.
  • In cited rat experiments, inhaled erionite caused mesothelioma in 27 of 28 rats, compared with 4 of 124 rats exposed to crocidolite.
  • The authors stated that mineralogical and pedigree studies in Cappadocian villages indicate the mesothelioma epidemic there is caused by erionite exposure in genetically predisposed individuals.
  • The authors stated there is no evidence of an association between mesothelioma and smoking.
• The authors' conclusion: The authors concluded that mesothelioma is an aggressive cancer caused by multiple factors that may work alone or in combination, and hoped that better understanding of its mechanisms will lead to new prevention and treatment strategies.

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, Epidemiology, Carcinogenesis, SEER, Carcinogenic, Mineral Fiber, erionite, Mesothelial Cells.

Related studies

• Iron overload as a major targetable pathogenesis of asbestos-induced mesothelial carcinogenesis — S. Toyokuni (2014)
• The pathogenesis of mesothelioma — M. Carbone, R.A. Kratzke, et al. (2002)
• The two-stage clonal expansion model in occupational cancer epidemiology: results from three cohort studies — A. Zeka, R. Gore, et al. (2011)
• 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)
• The epidemiology and pathogenesis of malignant mesothelioma — J.E. Craighead (1989)

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