Familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom, Western Australia

Our plain-English summary of Familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom, Western Australia, by N. de Klerk, H. Alfonso, N. Olsen, et al (International Journal of Cancer, 2013).

The study

• Authors: N. de Klerk, H. Alfonso, N. Olsen, A. Reid, J. Sleith, L. Palmer, G. Berry, A.B. Musk
• Journal: International Journal of Cancer
• Published: 2013;132(6):1423-8
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Clustering of cases of malignant mesothelioma within families has often been observed, but disentangling genetic and exposure effects has not been done. Former workers and residents exposed to crocidolite at Wittenoom, Western Australia, where many families shared exposure to asbestos, have had high rates of mesothelioma. Our study aimed to estimate the additional risk of mesothelioma in relatives, after allowance for common exposure to crocidolite. More than 11,000 former asbestos workers and residents from Wittenoom have been followed up in cancer and death registries. Levels of exposure for all members of the Wittenoom cohorts have been estimated previously. Relationships between family members of all mesothelioma cases were established from questionnaires, birth and death certificates. Expected numbers of cases of mesothelioma were estimated by fitting a Weibull survival model to all data, based on time from first asbestos exposure, duration and intensity of exposure and age. For each family group, the earliest case was considered the index case. Predicted risk was estimated for each subject from the time of diagnosis of the index case. Familial risk ratios were estimated by dividing observed cases by the sum of risks of all same degree relatives of index cases. There were 369 family groups with at least one case of mesothelioma and a further 25 cases of mesothelioma among relatives in the same families, with 12.9 expected. The risk ratio for blood relatives was 1.9 (95% confidence interval [CI] = 1.3-2.9, p = 0.002). These findings suggest an important, but not large, genetic component in mesothelioma, similar to many other cancers.

Copyright © 2012 UICC.

In plain English

This cohort study followed 6,694 former crocidolite (blue asbestos) miners and millers and 4,518 former residents of Wittenoom, Western Australia, to December 2006. The authors asked whether relatives of people with malignant mesothelioma had extra risk beyond what their own asbestos exposure predicted. Using each person's previously estimated exposure, they compared observed with expected cases among relatives of each family's first case; of 369 families with a case, 191 had more than one known member. Among blood relatives, 25 cases occurred against 12.9 expected (risk ratio 1.9, 95% confidence interval 1.3 to 2.9). The ratio was 1.8 (1.1 to 2.8) for first-degree and 2.6 (1.0 to 5.3) for second- or higher-degree relatives. Spouses had 2 cases against 3.4 expected (ratio 0.6; 0.1 to 2.1). A resampling check gave slightly lower ratios: 1.7 (1.0 to 2.4) for blood relatives, 1.5 (0.9 to 2.4) for first-degree and 2.2 (0.7 to 4.0) for second- or higher-degree relatives. The authors concluded the findings suggest an important, but not large, genetic component in mesothelioma. They noted small numbers, possible missed cases among emigrants, exposure-estimate errors, and crocidolite-only exposure.

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: Cohort study of familial risk. A statistical survival model (Weibull) predicted each person's mesothelioma risk from their asbestos exposure and age. Observed cases among relatives were then compared with the number expected from that model.
• Who was studied: 11,212 people with complete data from Wittenoom, Western Australia: 6,694 former miners and millers and 4,518 former town residents who did not work at the mine or mill. Follow-up ran to 31 December 2006. The familial analysis drew on the 369 families containing at least one mesothelioma case. In 178 of these, the index case had no known relatives, and those families contributed nothing to the familial comparison. That left 191 families with more than one member, 20 of which had more than one case.
• Exposure: Crocidolite (blue asbestos) mined at Wittenoom Gorge from 1943 to 1966. Exposure came from earlier estimates of: duration (days of exposure); cumulative exposure (fibres/millilitre years); and average intensity of exposure. Workers' estimates combined occupational and environmental exposure.
• Main results:
  • The whole cohort had 396 cases of malignant mesothelioma by the end of follow-up in December 2006.
  • All blood relatives of index cases: 25 observed cases versus 12.9 predicted. Risk ratio 1.9 (95% CI 1.3 to 2.9), p = 0.002. The bootstrap (resampling) estimate was 1.7 (1.0 to 2.4).
  • First-degree relatives (parent, sibling, child): 18 observed versus 10.2 predicted. Risk ratio 1.8 (95% CI 1.1 to 2.8), p = 0.017. The bootstrap estimate was 1.5 (0.9 to 2.4).
  • Second or higher degree relatives (aunt, uncle, cousin, grandparent, etc.): 7 observed versus 2.7 predicted. Risk ratio 2.6 (95% CI 1.0 to 5.3), p = 0.021. The bootstrap estimate was 2.2 (0.7 to 4.0). This ratio was higher than for first-degree relatives, but the difference was not statistically significant.
  • Spouses: 2 observed versus 3.4 predicted. Risk ratio 0.6 (95% CI 0.1 to 2.1), p = 0.85. The bootstrap estimate was 0.5 (0.0 to 1.4). Confidence intervals were wide under both methods.
• The authors' conclusion: The authors concluded that the findings suggest an important, but not large, genetic component in mesothelioma, similar to many other cancers. They added that this indicates a doubling of risk that may be attributable to genetic factors.
• Limitations the authors state:
  • The authors describe the analysis as a first and approximate look. Full pedigrees were not assembled for all families.
  • The results are based on small numbers.
  • Family members were assumed alive to the end of follow-up unless known to be dead or diagnosed. This could have biased the risk ratio downward, though the authors judged the effect likely small.
  • Cases may have been missed among people who emigrated from Australia to countries other than Italy.
  • Errors in exposure estimates, particularly at lower exposure levels, could have affected the expected numbers in an unknown way.
  • All subjects were exposed only to crocidolite, so the results might not extend to other forms of asbestos.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Wittenoom, Western Australia

All asbestos mines

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Wittenoom, Crocidolite, Mesothelioma, Death Certificate, Asbestos Exposure, confidence interval.

Related studies

• Malignant pleural and peritoneal mesotheliomas in former miners and millers of crocidolite at Wittenoom, Western Australia — G. Berry, N.H. de Klerk, et al. (2004)
• Malignant mesotheliomas in former miners and millers of crocidolite at Wittenoom (Western Australia) after more than 50 years follow-up — G. Berry, A. Reid, et al. (2012)
• Retinol supplementation and mesothelioma incidence in workers earlier exposed to blue asbestos (Crocidolite) at Wittenoom, Western Australia — H.S. Alfonso, A. Reid, et al. (2010)
• The additional risk of malignant mesothelioma in former workers and residents of Wittenoom with benign pleural disease or asbestosis — A. Reid, N. de Klerk, et al. (2005)
• Predicted mortality from malignant mesothelioma among women exposed to blue asbestos at Wittenoom, Western Australia — A. Reid, G. Berry, et al. (2009)
• Autoimmune antibodies and asbestos exposure: Evidence from Wittenoom, Western Australia — A. Reid, P. Franklin, et al. (2018)

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