Discussion
Overall, there have been no substantive changes in the time pattern of mesothelioma incidence in the United States since 1992. This conclusion would not be apparent if the current results using SEER data for 1973–2000 were compared with the results published by Price (7) that were based on SEER data for 1973 through 1992. That estimated model (7) showed a sharper decline in the number of annual male mesothelioma cases, projecting approximately 7,000 fewer cases between 2003 and 2054, than the model based on the most current data. However, a comparison to the Price results (7) would not be meaningful because of changes in SEER data and application of the cohort mortality rates used here. Therefore, it was necessary to reestimate the model using revised data through 1992 for comparison to the model based on current data through 2000. This comparison indicated no substantive change in the time pattern or number of future cases.
In addition to describing the time pattern of mesothelioma incidence, our results contain information about the potential effects of environmental exposures to asbestos and two related issues: 1) the existence of an exposure threshold and 2) the existence and magnitude of a background rate (i.e., mesotheliomas not associated with asbestos exposure). (In this discussion, threshold does not mean an exposure below which the risk of mesothelioma is zero; the threshold is an asbestos exposure level associated with a negligible incremental risk of mesothelioma.)
The constancy alone of the mesothelioma risk for females over time supports the existence of a threshold exposure. The effects, if any, of environmental exposures for the US population as a whole cannot be observed for males; as a group, males experienced high occupational exposures that masked low-exposure effects. In contrast, female exposures to asbestos have been primarily environmental. In the 1930s through the 1960s, women generally did not work in industries in which men experienced high levels of exposure to asbestos. For some women, exposures have been domestic (i.e., they live in households with men who were exposed occupationally), but the number of women with high levels of domestic exposure, although not zero, would have been relatively small. However, all women were exposed to asbestos in the environment, an exposure that would have increased since the 1930s, especially the dramatic increase during the 40-year period from 1930 to 1970 in the amount of asbestos used in US products (figure 2). As use increased, higher environmental exposures would have resulted from asbestos mining, manufacturing, and product use (e.g., vehicle brake systems, construction materials, and other asbestos-containing products) during this period and beyond for as long as the asbestos-containing products were in use.
Nevertheless, the mesothelioma risk for women has not increased. The age-adjusted mesothelioma rate for females was constant at an average of approximately 0.30 per 100,000 between 1973 and 1982, when it showed a one-time increase to 0.40 per 100,000 (figure 1). One might be tempted to interpret this change as a response to increasing environmental exposure. However, the female rate, which should have continued to increase after 1982 if the environmental exposure explanation is correct, remained constant after 1982. Therefore, the one-time mesothelioma increase for females does not indicate increasing exposure to asbestos in the environment but more likely a diagnostic effect. Environmental exposure levels, although increasing, have not triggered a risk response in women. Therefore, those exposure levels must have been below a threshold for mesothelioma.
A threshold higher than typical environmental asbestos exposures, as argued above, implies the existence of background mesotheliomas caused by agents other than asbestos that could account for most, if not all, female cases of mesothelioma. A number of studies provide evidence of background mesotheliomas (16–28). Simian virus 40 (SV40) is one of the nonasbestos agents that has been identified as a possible cause of mesothelioma (29, 30). Simian virus 40 was a contaminant in polio vaccines administered to 10–30 million people in the United States, mostly children, between 1955 and 1963 (30). It has not been determined whether simian virus 40 acting alone can cause mesothelioma (30). Our analysis does not indicate an increased risk in the 1955–1959 or 1960–1964 birth cohorts, those most likely to have received the contaminated vaccine (refer also to Strickler et al. (31)).
If all female cases of mesothelioma were unrelated to asbestos exposure, our analysis indicates that the lifetime background risk would be 3.6 x 10–4 (figure 3) and the current annual risk would be approximately 4 per million (over 5 per million if the population at risk is aged 20 years). These background risk levels would be upper bounds if a portion of female cases of mesothelioma were due to occupational, domestic, or unique high environmental exposures.
The background rates for females may not apply directly to males because the percentages of pleural and peritoneal mesotheliomas are different for men and women. In the SEER database, peritoneal mesotheliomas account for 7 percent of all mesotheliomas in males but 17 percent of all mesotheliomas in females. It is possible that peritoneal mesotheliomas in women are of two types but cannot be distinguished histologically: 1) those that are similar to mesotheliomas in males and 2) those that are unique, as evidenced in part by longer survival times of the cases (32; Andrew Churg, University of British Columbia, personal communication, 2002). On the basis of the differences between cases of mesothelioma in males and females, an adjustment to the background rates suggested above for females would be required if they were to be applied for males. For example, if all peritoneal mesotheliomas in females were excluded, the annual background rate for males would be 83 percent of the background rate for females.
The mesothelioma epidemic in the United States, which is beginning to recede, has been a consequence of ongoing high-level occupational exposure to asbestos from the 1930s through the 1960s in workplaces populated almost exclusively by males. Asbestos regulations promulgated by the US Occupational Safety and Health Administration (OSHA) in the early 1970s have led to dramatic reductions in exposure. These reductions are reflected in the pattern of mesothelioma incidence in the SEER data and were magnified through our modeling and analysis. It is unlikely that low environmental exposure to asbestos, or any other type of low-level asbestos exposure, is associated with more than a negligible risk of mesothelioma.