COMMITTEE APPROACH

To address the charge, a multidisciplinary committee was appointed by IOM that included experts in biostatistics, epidemiology, mineralogy, oncology, toxicology, and cancer biology. The committee interpreted its charge as requiring a comprehensive and systematic review of evidence on the cancer risk posed by asbestos at the specified sites in humans and in experimental animals. The committee also identified a need to review evidence related to the biologic plausibility of a causal association between asbestos and cancer at the designated sites. Relevant issues included the doses of asbestos fibers reaching the organs, persistence of fibers at the sites, potential interactions with target cells, and plausible mechanisms of carcinogenesis by asbestos fibers at the sites.

The committee was aware that fiber type may be a determinant of risk of developing mesothelioma (and possibly lung cancer) following asbestos exposure. The committee considered whether it should evaluate asbestos-associated risk for the designated cancers in terms of exposure to specific fiber types. In light of the almost universally mixed nature of actual occupational exposure, however, there was not sufficient evidence to have carried out such a review for the selected cancer sites. Consequently, the committee’s report describes the level of causal inference in relation to asbestos, without specifying the type.

Accordingly, the committee undertook a systematic review of the available human and toxicologic evidence, setting up a uniform approach for reviewing the full body of relevant epidemiological literature and for abstracting and synthesizing study results. The epidemiologic evidence comes from cohort (follow-up) studies of occupationally exposed persons and from case-control studies of the cancers that assessed occupational exposures as risk factors. The cohort studies generally addressed cancer mortality, and the case-control studies mostly considered incident cases. The studies were further classified by the method of exposure assessment. The results of the studies were then abstracted into a database for descriptive analysis and summary with the technique of quantitative meta-analysis. The units of input for the meta-analysis on each selected cancer site were the most comprehensive risk estimates available on discrete study populations, so a single citation might generate more than one datum (such as separate results for men and women), whereas only the final follow-up results would be used for a series of publications on the same occupational cohort. The meta-analysis on each dataset yielded a summary estimate of cancer risk at the anatomical site associated with asbestos exposure with a confidence interval that accounts for sampling variation within each study and for variation in relative risk among studies. The committee also reviewed the toxicologic literature and the extensive experimental literature on carcinogenesis by



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