Mesothelioma mortality in asbestos workers: implications for models of carcinogenesis and risk assessment

Our plain-English summary of Mesothelioma mortality in asbestos workers: implications for models of carcinogenesis and risk assessment, by J. Peto, H. Seidman, I.J. Selikoff (British Journal of Cancer, 1982).

The study

• Authors: J. Peto, H. Seidman, I.J. Selikoff
• Journal: British Journal of Cancer
• Published: 1982;45(1):124-35
• Cited by: 213 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 000703).

Abstract

Mesothelioma death rates in asbestos workers appear to be proportional to the 3rd or 4th power of time from first exposure under a wide range of conditions of exposure for both pleural and peritoneal tumours, though the peritoneal:pleural ratio depends on fibre dimension and type. Age at first exposure has little or no influence, however, which supports the "multi-stage" model of carcinogenesis under which the increase in most cancer incidence rates with age is due to a constant incidence of genetic or epigenetic accidents, rather than to progressive generalized changes in regulatory or immune function. These relationships provide a simple basis for risk assessment, and support the suggestion that mesotheliomas may constitute a high proportion of cancer deaths resulting from early exposure to asbestos.

In plain English

The authors analysed mesothelioma deaths among 17,800 members of the International Association of Heat and Frost Insulators and Asbestos Workers, monitored 1967 to 1979. They then fitted the same model to four other published cohorts. Among insulation workers, 87 pleural and 149 peritoneal mesotheliomas occurred up to age 80. Death rates depended on time since first exposure; age at first exposure had little or no influence. For men first employed 1922 to 1946, rates rose roughly as time since exposure to the power 3.20, which the authors generalised as between 3 and 4. Allowing for other causes of death, this fitted rate predicted that about 15% of men first exposed at age 20 under such conditions would die of mesothelioma before 80. Exposure from age 50 under similar conditions gave a predicted risk below 1%. Peritoneal tumours made up 63% of the insulation workers' mesotheliomas but none among chrysotile miners, crocidolite miners or chrysotile factory workers. The authors concluded that the findings support the "multi-stage" model of cancer. They also judged comparisons between fibre types almost meaningless without detailed exposure data.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Analysis of cohort mortality data for insulation workers, with the same time-since-exposure model also fitted to four other published cohort studies of asbestos workers
• Who was studied: 17,800 members of the International Association of Heat and Frost Insulators and Asbestos Workers (North America), with mortality monitored 1967 to 1979. Comparison cohorts were English factory workers, English chrysotile textile factory workers, Australian crocidolite miners and U.S. amosite factory workers.
• Exposure: Occupational asbestos exposure as insulation workers, analysed by age at first exposure and time since first exposure. Comparison cohorts were exposed to amosite, to crocidolite, to chrysotile, or to a mix of amosite, crocidolite and chrysotile.
• Main results:
  • Among the insulation workers, 87 pleural and 149 peritoneal mesotheliomas were observed up to age 80.
  • In insulation workers, observed and expected numbers of mesothelioma deaths matched closely for both pleural and peritoneal sites regardless of age at first exposure. The authors described age at first exposure as having little or no influence.
  • Among insulation workers first employed 1922 to 1946, the estimated exponent of time since first exposure was 3.20 (standard error 0.36) and the constant b was 4.37 x 10-8. Earlier and later recruits appeared to have had lower risk.
  • Using the fitted rate for insulation workers first employed 1922 to 1946, the authors calculated an annual mesothelioma death rate of 2.3 per 1000 at 30 years after first exposure. Allowing for increases in other asbestos-related death rates, they predicted a risk of about 15% of dying of mesothelioma before age 80 for men first exposed at age 20. For exposure under similar conditions from age 50, the predicted lifelong risk was less than 1%.
  • In the other cohorts, the fitted model matched observed deaths satisfactorily beyond 15 years after first exposure. Below 15 years, death rates may have been lower than predicted.
  • Peritoneal tumours made up 49% (22/45) of mesotheliomas among factory workers exposed to amosite and other fibres, 63% (149/236) among insulation workers and 67% (6/9) among Canadian crocidolite gas-mask assemblers. There were none among chrysotile miners, crocidolite miners or factory workers exposed principally to chrysotile. The authors said amphiboles appear largely responsible for asbestos-related peritoneal mesothelioma.
  • The pleural mesothelioma death rate among U.S. insulation workers was about half that in the factory cohorts. Among Australian crocidolite miners it was twice that of factory workers and more than 3 times that of insulation workers.
  • Among insulation workers who smoked and were first exposed under age 25, there were 99 mesotheliomas and 211 lung cancer deaths against 32.67 expected (relative risk 6.5). The ratio of asbestos-induced lung cancer to mesothelioma was 3.9 among smokers first exposed at age 25 or over, 1.8 among smokers first exposed below age 25, and 0.2 among non-smokers.
• The authors' conclusion: The authors concluded that mesothelioma death rates rise roughly as time since first exposure to a power between 3 and 4, with little or no influence of age at first exposure. In their view, this supports the multi-stage model of carcinogenesis and provides a simple basis for risk assessment.
• Limitations the authors state:
  • Observed mesothelioma rates more than 40 years after first exposure may be too low because of underdiagnosis in old age.
  • Without detailed data on duration and level of exposure, comparisons between fibre types are almost meaningless.
  • The overall death rates for insulation workers may not reflect the pattern in a single cohort, because different time periods were based on men first exposed in different eras.
  • Expected numbers less than 15 years after first exposure were consistently too high under the fitted model.
  • The power-law pattern may not be established securely enough to support any particular model of carcinogenesis.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Carcinogenesis, Incidence.

Related studies

• Lung cancer in chrysotile asbestos workers: analyses based on the two-stage clonal expansion model — D.B. Richardson (2009)
• Time-related factors in quantitative risk assessment — K.S. Crump, B.C. Allen, et al. (1987)
• Dose-response relationships for asbestos-related disease: implications for hygiene standards. Part II. Mortality — J. Peto (1979)
• Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite for mesothelial carcinogenesis — D. Aierken, Y. Okazaki, et al. (2014)
• Occam's razor pares the choice among statistical models — K.J. Rothman (1978)
• Occupational risk factors for mortality from stomach and lung cancer among rubber workers: an analysis using internal controls and refined exposure assessment — K. Straif, L. Chambless, et al. (1999)

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