Etiology
A unique feature of mesothelioma is its strong relationship with asbestos exposure, which has recently led to great public concern in view of the ubiquitous presence of that mineral.
Epidemiologic and Clinical Evidence of the Role of Asbestos
Many epidemiologic surveys around the world have revealed prior exposure to asbestos in about 70 to 80% of all cases of mesothelioma when a careful history was taken.16,63,192,305 Beginning 15 years after onset of exposure, about 6% of asbestos workers over the age of 35 years die of mesothelioma.238 The death rate from mesothelioma in a cohort of asbestos insulation workers was 344 times higher than in the general population.236
It is estimated that, from 1940 through 1979, approximately 27.5 million workers were occupationally exposed to asbestos in the United States, with a calculated annual death rate from mesothelioma of about 2,000 in 1980 up to 3,000 in the late 1990s.190 Exposure can be not only occupational but also environmental, or even familial by household contamination. The latter type of exposure, usually through the work clothes of an asbestos worker, is an important factor for women. It was also found in 5 of 10 young adults (40 years or younger) with mesothelioma who had been exposed in childhood.134 Insulation, construction, shipyard industries, and automobile brakes are among the many sources of occupational exposure. The delay between first exposure and onset of the disease is extremely long, averaging 30 to 45 years, with a usual range of 10 to 65 years and a standard deviation of 12 years.63,238,305 Because of such a delay, asbestos exposure can easily be underestimated, since occupational histories are often inadequately documented.
197,280 Moreover, exposure may have been short or minimal, 63,238 although sometimes a very short exposure may have been intense.306 Pulmonary asbestosis and fibrosis are often absent or are rarely severe and are found at autopsy in about 40% of patients with mesothelioma.16,63 Due to the long latency and to the vastly increased use of asbestos during and after World War II, the incidence of mesothelioma is expected to continue to increase.190 Although asbestos exposure and cigarette smoking act synergistically to produce bronchogenic carcinoma, smoking is not a factor for mesothelioma.183,192,238,291 The presence of asbestos fibers in sections of lung tissue is another proof of asbestos exposure. Asbestos fibers are more difficult to detect in mesothelioma tissues than in the pulmonary parenchyma. Fibers in tissues can acquire a proteinaceous coating containing iron, leading to the formation of ferruginous bodies.238 These are not specific and can be called asbestos bodies only if the central core is identified as being asbestos. The asbestos minerals are divided into two major categories: the serpentines (chrysotile) with a general formula Mg3Si2O5(OH)4, forming long hollow tubes, and the amphiboles containing more silica and less magnesium oxide and forming short, straight fibers.238 Among the various types of asbestos associated with mesothelioma, amphiboles carry the highest risk: crocidolite in South Africa, and amosite in the United States have been most commonly incriminated.
127,183,293 Chrysotile, a long, curly fiber with poor pulmonary penetration which can be dissolved in lung tissue, seems to carry a much lower risk, although it does not appear to be nil.68,218,293 It has been postulated that mesotheliomas occurring in chrysotile-exposed individuals may be related to contamination by tremolite,68 another amphibole fiber which has been implicated in cases of mesothelioma in Greece,150 and which may contaminate other substances, such as talc or vermiculite.177 On the other hand, another amphibole fiber mined in Finland, anthophyllite, a thick coarse fiber, has been shown to cause calcified pleural plaques but usually not mesothelioma.127
These data emphasize the importance of the type of fiber and its physical characteristics and also the fact that most natural asbestos fibers are rarely pure but mixed.127 Although asbestos fibers can be detected in essentially 100% of the lungs of city dwellers by using special techniques,151 their number is markedly greater in the lungs of patients with mesothelioma and occupational exposure to asbestos, commonly reaching several million fibers per gram of dry weight.16 This is particularly true when amphibole fibers are counted.183 The mean increase of lung fiber burden of mesothelioma patients as compared with controls was seven times higher for pleural and 16 times higher for peritoneal mesothelioma but was lower than for patients with asbestosis (48 times higher than controls) or lung cancer with asbestos exposure (32 times higher than controls).
293 The question of a dose-response relationship between exposure to asbestos and occurrence of mesothelioma has been suggested by indirect methods, such as duration of employment in asbestos factories, or by quantitative measurements of pulmonary asbestos burden,63 especially if amphibole fibers > 10 microns are considered.218 No safe threshold has been established for asbestos exposure, however, and the asbestos burden in the lungs of mesothelioma patients forms a continuum that totally overlaps with controls at the lower end.
Asbestos Exposure - Asbestosis, Fibrosis
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