© 2005 American Thoracic Society doi: 10.1164/rccm.2507003
Can Exposure to Very Low Levels of Asbestos Induce Pleural Mesothelioma?INSERM Unité 687-IFR69, Saint Maurice, France Asbestos is a recognized human carcinogen, causally related to pleural and peritoneal mesothelioma and to lung cancer (1). Mesothelioma is of particular interest, as it is a specific outcome of asbestos exposure and no other causal factor except for exposure to asbestos (and erionite, a naturally occurring mineral fiber found in Turkey) (2) has been established or even convincingly suspected. The vast majority of asbestos-induced mesotheliomas in the industrialized world is caused by occupational asbestos exposure, and occurs among workers engaged in extracting and manufacturing asbestos, or performing tasks involving contact with asbestos-containing materials (3). Concern used to be focused on the occupational environment, but it is now recognized that asbestos fibers are widely distributed in the general environment. Persons can be exposed to asbestos in different nonoccupational circumstances: living with asbestos workers, with regular exposure to soiled work clothes brought home; environmental exposure in the neighborhood of industrial sources (asbestos mines and mills, asbestos processing plants); passive exposure in buildings containing asbestos; and natural environmental exposure to geological sources (4). Studying the effects of nonoccupational asbestos exposure on mesothelioma risk is important because it could provide information about the nature of the exposure–response relationship that cannot be obtained from studies of workers whose exposures begin in adulthood, are limited to working hours, are typically much higher in concentration, and who are mainly male. Natural environmental exposure to geological sources is of special interest, since populations subjected to natural sources present specific temporal exposure characteristics: exposure can start during childhood and be lifelong, and it can occur around the clock, seven days a week. Evidence on environmental exposure of natural origin thus provides information about the effect of early exposure on cancer risk and on latency periods, susceptibility according to sex, or the potentially different effect of asbestos fiber types (chrysotile, or amphiboles such as crocidolite, amosite, or tremolite, which are considered to be more potent carcinogens for mesothelioma than chrysotile fibers). The main findings of studies in rural areas of Turkey (5), Greece (6), some Mediterranean islands (7–9), China (10), and New Caledonia (11), where occupational exposure to asbestos is rare, even nonexistent, show that asbestos exposure starting at birth does not seem to influence the latency period of mesothelioma. The data also indicate that susceptibility does not differ according to sex, and confirm that the much higher rates of mesothelioma among males in the industrialized countries are most probably due to sex differences in occupational exposure to asbestos. Studies of mesothelioma related to environmental exposure to geological sources of asbestos have yielded important findings. However, some important issues remain unresolved. Thus, it would be of utmost importance, from a scientific and public health point of view, to know whether exposure to low levels of asbestos is able to induce pleural mesothelioma. There is still controversy regarding this question (12, 13). While exposure in environmental settings is generally much lower than in occupational circumstances, the levels may not be negligible. In studies in which elevated risk of mesothelioma was demonstrated, people typically lived in close vicinity of naturally occurring asbestos sources, and may have had direct contact with asbestos, when whitewashing houses with material containing asbestos or working in polluted fields. It is thus likely that lifelong cumulative exposure may have been as high (if not higher) as in some occupational settings, but it was not—or not adequately—measured, and nonoccupational studies have not yet provided adequate answers. This is why the work of Pan and coworkers, reported in this issue of the Journal (pages 1019–1025) (14), showing a relationship between mesothelioma risk and residential distance from naturally occurring asbestos, and suggesting that there is an excess risk of mesothelioma even at a long distance from the asbestos source, is important. To our knowledge, this study is the first one that demonstrates such an effect quite convincingly. While this study has some limitations (occupational exposure was only partially taken into account, no residential history was available for the subjects, no cases under 35 years of age could be included, and asbestos exposure was indirectly assessed), many features are strong. It relied on a register-based selection of a very large number of mesothelioma cases, and their localization was quite precise, thanks to the geocoding of residency and to the use of advanced GIS techniques. The results show a convincing internal consistency. The role of occupational exposure is clear and the risk varies with exposure, showing that even if it was not completely controlled for, the study captures its main effect. There was a linear relationship between distance and the pleural mesothelioma risk, still evident when different methods were used or when restricted to some subgroups; the distance–effect relationship was similar among men and women, even if not statistically significant among the latter due to smaller numbers. Pan and colleagues (14) bring new findings in favor of the carcinogenic role of low levels of exposure to asbestos, as it is most likely that level of exposure to asbestos at the remote distances where excess risk of pleural mesothelioma was apparent is very low. The fact that the risk of peritoneal mesothelioma, which is induced by higher exposure than pleural mesothelioma (1), is not related to the distance of the asbestos source gives more weight to the hypothesis that very low levels of asbestos may cause mesothelioma of the pleura. Additional work is now necessary for an accurate assessment of the levels of cumulative exposure that people experience in areas where an excess risk of pleural mesothelioma was observed. FOOTNOTES Conflict of Interest Statement: Neither of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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