ScienceWeek Medicine

2004 May #8

On Malignant Mesothelioma

The following points are made by M. Carbone and M.A. Rdzanek (Clin Lung Cancer. 2004 Suppl 2:S46):

1) 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.

2) 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.

3) 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.

4) 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.

Clinical Lung Cancer http://www.asco.org

--------------------------------Related Material:

Low Level Asbestos Exposure: Dangerous or Not Dangerous?

Asbestos is a commercially relevant group of strong, ductile, and fire-resistant mineral fibers. These properties, which differ among different mineralogic types of asbestos, strongly affect its in vivo persistence and toxicity. Chrysotile asbestos constitutes approximately 99 percent of airborne asbestos fibers in the general environment. Heavy industrial exposure to asbestos causes lung cancer and mesothelioma (a cancer of one of the layers of cells lining various body cavities), but it is not clear whether much lower environmental exposure to asbestos also causes these cancers. Various regulatory agencies have estimated the risk of cancer from low asbestos exposure by extrapolating from the data for high asbestos exposure.

Camus et al (New England J. Med. 1998 338:1565)

1) The authors tested the prediction model used by the US Environmental Protection Agency (EPA), by examining the predicted risk of asbestos-induced lung cancer in a population of women with relatively high levels of nonoccupational exposure to asbestos. Mortality among women in 2 chrysotile-asbestos mining areas of the province of Quebec (CA) was compared with mortality among women in 60 control areas. The EPA model, applied to the measured asbestos concentrations in the local air, predicts approximately 75 excess deaths from lung cancer in the mining-area population.

2) The authors report their study indicates between 0 and 6.5 excess deaths from lung cancer in the population (relative risk = 1.0). The authors conclude they found no measurable excess risk of death due to lung cancer among women in two chrysotile-asbestos mining regions, and that the EPA model overestimated the risk of asbestos-induced lung cancer by at least a factor of 10.

In an editorial rebuttal to this paper, P.J. Landrigan (New England J. Med. 1998 338:1618) makes the following points:

1) All forms of asbestos are carcinogenic. All have been shown in clinical, epidemiologic, and laboratory studies to be fully capable of causing lung cancer, mesothelioma, and the full range of asbestos-related diseases. All forms appear to be equipotent in the capacity to cause cancer of the lung.

2) The most plausible explanation of the low mortality from lung cancer observed in the Camus et al study is that the women in the mining areas were exposed to an asbestos aerosol in which many particles were too large to reach their lungs. Previous studies have indeed established that the risk of cancer in the mining and milling industry is much lower than that in the industries that process and use asbestos, such as textile manufacture and insulation. In mining and milling, many large asbestos particles are suspended in the air, and they tend not to reach the pulmonary alveoli as efficiently as small particles. Thus, air sampling based on light microscopy in the mining environment produces a spuriously high estimate of true alveolar exposure.

3) Landrigan says: "Camus et al go beyond their data when they assert, without qualification, that the EPA's model overestimates the risk of lung cancer among persons with nonoccupational exposure to asbestos by at least a factor of 10. The EPA's current regulatory controls embody a level of caution commensurate with the hazard."

4) Chrysotile-asbestos is still indisputably a human carcinogen, and this is also true for Canadian chrysotile. Camus et al did, in fact, find the risk of lung cancer associated with residence in the asbestos mining areas to be more than 7 times that in non-mining areas (standardized mortality ratio = 7.63). Landrigan concludes: "Assertions that chrysotile can be used without risk in developing nations are contrary to fact and extremely dangerous."

New Engl. J. Med. http://www.nejm.org

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