Malignant mesothelioma: facts, myths, and hypotheses

Our plain-English summary of Malignant mesothelioma: facts, myths, and hypotheses, by M. Carbone, B.H. Ly, R.F. Dodson, et al (Journal of Cellular Physiology, 2012).

The study

• Authors: M. Carbone, B.H. Ly, R.F. Dodson, I. Pagano, P.T. Morris, U.A. Dogan, A.F. Gazdar, H.I. Pass, H. Yang
• Journal: Journal of Cellular Physiology
• Published: 2012;227(1):44-58
• Type of article: Review
• Cited by: 282 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is a neoplasm arising from mesothelial cells lining the pleural, peritoneal, and pericardial cavities. Over 20 million people in the US are at risk of developing MM due to asbestos exposure. MM mortality rates are estimated to increase by 5-10% per year in most industrialized countries until about 2020. The incidence of MM in men has continued to rise during the past 50 years, while the incidence in women appears largely unchanged. It is estimated that about 50-80% of pleural MM in men and 20-30% in women developed in individuals whose history indicates asbestos exposure(s) above that expected from most background settings. While rare for women, about 30% of peritoneal mesothelioma in men has been associated with exposure to asbestos. Erionite is a potent carcinogenic mineral fiber capable of causing both pleural and peritoneal MM. Since erionite is considerably less widespread than asbestos, the number of MM cases associated with erionite exposure is smaller. Asbestos induces DNA alterations mostly by inducing mesothelial cells and reactive macrophages to secrete mutagenic oxygen and nitrogen species. In addition, asbestos carcinogenesis is linked to the chronic inflammatory process caused by the deposition of a sufficient number of asbestos fibers and the consequent release of pro-inflammatory molecules, especially HMGB-1, the master switch that starts the inflammatory process, and TNF-alpha by macrophages and mesothelial cells. Genetic predisposition, radiation exposure and viral infection are co-factors that can alone or together with asbestos and erionite cause MM. J. Cell. Physiol. 227: 44-58, 2012. © 2011 Wiley Periodicals, Inc.

Copyright © 2011 Wiley Periodicals, Inc.

In plain English

This article reviewed mesothelioma incidence, asbestos and erionite, possible co-factors, exposure history and diagnosis. It also reported the authors' lung tissue analysis of 38 pleural mesothelioma patients (8 women, 30 men) seen for care unrelated to litigation. By electron microscopy, they counted chrysotile, amosite, crocidolite, tremolite and anthophyllite fibers. They compared counts with questionnaire histories, treating over 0.5 million fibers per dry gram as exposed. They called this cut-off arbitrary and said classifying levels between 0.5 and 1.0 million was subjective. By that cut-off, 25 of the 38 were exposed. Eleven of the 18 reporting no exposure were above it; 6 of the 20 reporting exposure had only background levels. The authors found a lack of association between lung levels and reported history. The women were on average 14 years younger at diagnosis than the men, without higher fiber amounts. They concluded that histories, even from trained personnel, may be unreliable for individuals, and that factors other than asbestos appear to be the main cause of mesothelioma in women. They noted that they had too few women for a definitive conclusion.

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: Review article. It also includes the authors' own lung fiber-content analysis of surgical lung biopsies from mesothelioma patients, compared with questionnaire exposure histories.
• Who was studied: 38 patients diagnosed with pleural malignant mesothelioma (8 women, 30 men) whose lung tissue was surgically resected. They were seen for analyses and treatment unrelated to litigation.
• Exposure: Lung asbestos fiber burden (chrysotile, amosite, crocidolite, tremolite, anthophyllite), in millions of fibers per gram, measured by analytical transmission electron microscopy. This was compared with exposure history from the American Thoracic Division of Lung Disease Adult questionnaire. Of the 4 women who reported exposure, 3 reported household exposure through a father and 1 possible exposure through contaminated talcum powder.
• Main results:
  • 25 of the 38 patients (21 men and 4 women) had total asbestos levels above 0.5 million fibers per dry gram, the authors' chosen cut-off for 'exposed'
  • Of the 18 patients who reported no asbestos exposure, 11 (3 women and 8 men) had levels above the cut-off. The authors described only 7 as truly unexposed.
  • Of the 20 patients who reported exposure (16 men, 4 women), 6 (3 men and 3 women) had only background lung asbestos levels
  • The authors found a lack of association between measured lung asbestos levels and reported exposure history (chi-square 0.33, P = 0.56)
  • The 8 women were on average 14 years younger than the men at diagnosis (P = 0.001), and their asbestos amounts did not exceed those of the men
  • Under stricter definitions, only 18 of 38 would count as exposed. This was true both when counting amphiboles only above 0.5 and when using total fibers above 1.0.
  • 20 of the 38 mesotheliomas contained SV40 virus sequences, including 3 of the 8 women. There was no significant correlation with asbestos exposure.
• The authors' conclusion: The authors concluded that even histories taken by trained personnel and according to established guidelines may be unreliable at the individual level. Their overall conclusion was that pleural mesothelioma in men is strongly associated with asbestos exposure, that about 30% of mesothelioma in women is associated with asbestos exposure, and that factors other than asbestos appear to be the main cause of mesothelioma in women.
• Limitations the authors state:
  • The study included too few women to reach a definitive conclusion about sex differences
  • Lung fiber burden reflects only what remains at sampling, after clearance and movement of inhaled fibers
  • The 0.5 million fibers per dry gram cut-off for 'exposed' was chosen arbitrarily, lowered from the laboratory's usual 1.0
  • Levels between 0.5 and 1.0 million fibers per gram are at the upper limits of background, and the authors described classifying them as exposed or background as subjective

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, Neoplasm, Mesothelial Cells, Pericardial, Asbestos Exposure, Peritoneal Mesothelioma, erionite, Carcinogenic.

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