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Asbestos: Selected Cancers 1 Introduction STATEMENT OF CHARGE As contracted through the National Institutes of Health, the committee’s charge reads: The Institute of Medicine (IOM) Board on Population Health and Public Health Practices will oversee a study that will comprehensively review, evaluate, and summarize the peer-reviewed scientific and medical literature regarding the association between asbestos and colorectal, laryngeal, esophageal, pharyngeal, and stomach cancers. Based on its examination and evaluation of the extant literature and other information it may obtain in the course of the study, the committee will determine if there is a causal association between asbestos and colorectal, laryngeal, esophageal, pharyngeal, or stomach cancers. CURRENT LEGISLATION The committee’s charge to determine whether asbestos may play a causal role in the occurrence of cancer at the five specified sites was drawn directly from Senate Bill 852, the Fairness in Asbestos Injury Resolution (FAIR) Act. The bill would establish an industry-underwritten $140 billion trust fund for orderly compensation of people suffering health consequences of working with asbestos or of living in Libby, Montana. The legislation as reported out of the Senate Committee on the Judiciary (April 19, 2005) defines asbestos to include: (A) chrysotile; (B) amosite; (C) crocidolite; (D) tremolite asbestos; (E) winchite asbestos; (F) richterite asbestos; (G) anthophyllite asbestos; (H) actinolite as-
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Asbestos: Selected Cancers bestos; (I) asbestiform amphibole minerals; (J) any of the minerals listed under subparagraphs (A) through (I) that has been chemically treated or altered, and any asbestiform variety, type, or component thereof; and (K) asbestos-containing material, such as asbestos-containing products, automotive or industrial parts or components, equipment, improvements to real property, and any other material that contains asbestos in any physical or chemical form. People who have a diagnosis of asbestosis, lung cancer, or mesothelioma will be eligible to file a claim documenting their asbestos exposure. Eligibility may also be extended to any additional cancers that are found to be causally associated with asbestos by the report of the present IOM expert committee delineated as item (e) under Subtitle C, Section 121—Medical criteria. The IOM report will be binding on the administrator and the physicians’ panel that processes claims against the trust fund. The pending legislation was reported out of the Committee on the Judiciary on June 16, 2005, and was expected to be voted on early in 2006. Asbestos fibers are known to be carcinogenic. The uniqueness and completeness of the carcinogenic activity of asbestos in mesothelial tissues is clear and undisputed. Most cases of mesothelioma are attributable to asbestos exposure. The role of asbestos in producing lung cancer, particularly in smokers, is also clear. Cancers at the sites included in the charge are largely of epithelial origin, so the underlying causal mechanism would be expected to be similar to that of lung cancer. Inasmuch as the determination of asbestos (in its various forms) as a human carcinogen is long established on the basis of findings of epidemiologic investigations and supportive animal and in vitro studies, this committee viewed its charge to be a more focused evaluation of whether asbestos causes cancer in particular organs. “Biologic plausibility” has been shown for asbestos’ carcinogenic potential in general, so this committee’s criteria for site-specific causality will differ somewhat from the determinations of whether an agent is a generic human carcinogen, as conducted by the International Agency for Research on Cancer and the US Environmental Protection Agency, for example. OVERVIEW OF PATTERNS OF ASBESTOS USE AND RECOGNITION OF ITS HEALTH CONSEQUENCES The physical and chemical properties of minerals classified as asbestos (see Chapter 3) have led to widespread applications of these fibrous substances beginning as long as 2,000 years ago. Those properties include heat stability and fire resistance, thermal and electric insulation, resistance to wear and friction, tensile strength and weavability, and resistance to chemical and biologic degradation (HHS 2004). Uses of asbestos burgeoned as the modern industrial era gained momentum in the 1880s, and industrial consumption peaked in the United States in 1973 (Virta 2002). The gradual
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Asbestos: Selected Cancers recognition that this useful substance was associated with the occurrence of serious health consequences led to increasingly strict curtailment of asbestos’s industrial use, but the epidemic of asbestos-caused disease is far from over. Because of the sustained period over which millions of workers were exposed to asbestos in mining, production, and construction and the decades-long latent period of development of asbestos-caused diseases, new cases of these debilitating and often fatal consequences of exposure will continue to be diagnosed for many years to come. A number of adverse health outcomes are now causally associated with exposure to asbestos. An approximate timeline for recognition of the adverse consequences is provided in this section, as drawn from published sources. The first to be recognized was asbestosis, a pneumoconiosis characterized by fibrosis of the lung and reduction of lung function (Table 1.1), first reported as early as 1907 (Hamilton and Hardy 1974, as cited in Becklake 1976). Iron-coated fibers, called asbestos bodies, are typically found in the tissues of affected lungs. Mesothelioma, an uncommon tumor of the pleural and peritoneal mesothelium (tissues lining the thoracic and abdominal cavities and the organs in them), was linked to asbestos in the early 1960s in clinical case reports, and the increased risk was then further shown in cohort studies of asbestos workers. In the 1950s, epidemiologic studies documented the association of lung cancer with asbestos exposure, and the risk was found to be particularly increased in exposed workers who smoked. As worker cohorts were followed and their cancer risks were tracked, concern arose that asbestos might cause other types of cancers. Complementary information on these cancer sites was reported from studies that assessed site-specific cancer risk in relation to occupational exposures in general; asbestos exposure was specifically addressed in many of these case-control studies. The epidemiologic information is further complemented by an extensive toxicologic literature that includes animal bioassays and investigation of mechanisms of disease production. Since the first rec- TABLE 1.1 Timeframe for Recognition of Various Health Effects Associated with Asbestos Exposure Health Effect Suspected Probable Established Asbestosis ~ 1900 ~ 1915 ~ 1930 Lung cancer ~ 1930 ~ 1945 ~ 1955 Mesothelioma ~ 1940 ~ 1955 ~ 1965 Other cancers ~ 1955 ~ 1970 ? SOURCE: Becklake (1976), Liddell (1997), Ross and Nolan (2003).
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Asbestos: Selected Cancers ognition that asbestos can cause cancer in humans, experimental studies have revealed multiple mechanisms that may contribute to asbestos-related diseases. COMMITTEE’S APPROACH TO ITS CHARGE The extensive literature related to the carcinogenic potential of asbestos, including a substantial body of epidemiologic studies plus numerous toxicologic and mechanistic studies, had to be considered in defining the portion relevant to the committee’s charge. The committee interpreted its charge as requiring a comprehensive and systematic review of existing evidence on asbestos-related cancer risk at the specified sites in humans and in experimental animals. Accordingly, the committee undertook a systematic review of the available evidence, setting up a uniform approach for reviewing the literature and for abstracting and synthesizing study results. Because the committee’s charge requires a determination of whether asbestos “causes” cancer at the specific sites, the committee considered various guidelines for causal inference and the terminology for classifying the strength of evidence in support of causation. That review led to the application of guidelines for causal inference based on the widely applied criteria proposed by Hill (1965) and similar criteria used in the reports of the US surgeon general on smoking and health (HEW 1964, HHS 2004). The committee selected a four-level classification of the strength of evidence for causal inference: sufficient, suggestive but not sufficient, inadequate, and suggestive of no relationship. In addition to searching the published literature systematically, the committee invited experts in several relevant fields to make presentations and provide background information, as indicated in the agendas for open sessions presented in Appendix A. The topic of asbestos and cancer has many facets, including the influence of fiber type on risk and the interactions of asbestos with other factors that produce cancer at the same sites, such as tobacco-smoking as a cause of cancer of the larynx. The committee did not consider the issue of fiber type, which was not included in its charge; it did consider information on the combined effect of asbestos with other risk factors when such information was available. The committee did not attempt to quantify the risk of cancers at the selected sites; that potentially extensive effort was also beyond the charge. The committee took into account the limitations of the available epidemiologic information, a key component of the evidence reviewed. The epidemiologic characteristics of the cancers to be investigated (pharyngeal, laryngeal, esophageal, stomach, and colorectal) were considered, including incidence and mortality, survival, and risk factors that might potentially confound or modify the associations of asbestos with risks of cancers at
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Asbestos: Selected Cancers these sites. In any systematic review, another concern is publication bias that may arise from potentially slanted decisions, ranging from researchers’ choices of what to study and report, to the tendency of the publication process itself to select for positive findings. REFERENCES Becklake M. 1976. Asbestos-related diseases of the lung and other organs: Their epidemiology and implications for clinical practice. American Review of Respiratory Disease 114(1): 187-227. Hamilton A, Hardy H. 1974. Industrial toxicology. In: Asbestos-Related Diseases of the Lung and Other Organs: Their Epidemiology and Implications for Clinical Practice. 3rd edition. Acton, MA: Publishing Sciences Group, Inc. Pp. 421. HEW (US Department of Health Education and Welfare). 1964. Smoking and Health: Report of the Advisory Committee to the Surgeon General. Washington, DC: US Government Printing Office. HHS (US Department of Health and Human Services). 2004. Asbestos CAS No. 1332-21-4. In: 11th Report on Carcinogens. Washington, DC: National Toxicology Program. Hill A. 1965. The environment and disease: Association or causation? Proceedings of the Royal Society of Medicine 58: 295-300. Liddell F. 1997. Magic, menace, myth and malice. Annals of Occupational Hygiene 41(1): 3-12. Ross M, Nolan R. 2003. History of asbestos discovery and use and asbestos-related disease in context with the occurrence of asbestos within ophiolite complexes. Geological Society of America Special Paper 373: 447-470. Virta RL. 2002. Asbestos. Mineral Yearbook. Reston, VA: US Geological Survey.
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