Genetic susceptibility to malignant mesothelioma and exposure to asbestos: the influence of the familial factor

Our plain-English summary of Genetic susceptibility to malignant mesothelioma and exposure to asbestos: the influence of the familial factor, by D. Ugolini, M. Neri, M. Ceppi, et al (Mutation Research, 2008).

The study

• Authors: D. Ugolini, M. Neri, M. Ceppi, A. Cesario, I. Dianzani, R. Filiberti, F. Gemignani, S. Landi, C. Magnani, L. Mutti, R. Puntoni, S. Bonassi
• Journal: Mutation Research
• Published: 2008;658(3):162-71
• Type of article: Review
• Cited by: 37 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Asbestos is the principal etiological factor of malignant mesothelioma (MM), accounting for more than 80% of all tumor cases. However, other co-factors, including genetic susceptibility may play a role in the etiology of this disease, possibly modulating the effects of exposure to asbestos and other carcinogenic mineral fibers. The frequent report of familial clustering was the first indication supporting the involvement of genetic factors. Therefore, we performed an extensive literature search to evaluate existing studies reporting familial cases of MM.

Methods: Published reports addressing the issue of familial susceptibility to MM have been searched through PubMed using keywords and free text tools. Eighty-two citations were retrieved and 20 of them actually reported a familial cluster of MM. Three more articles were identified through the references. The probability that the observed familial clusters of mesothelioma could have randomly occurred in exposed families was evaluated with the Family History Score Zi (FHSi).

Results: The result of this analysis suggested that clustering of MM cases in families exposed to asbestos may be explained with the additional contribution of other familial factors. The FHSi allowed to reject the hypothesis of random occurrence of these clusters with a probability of a first type error ranging between 1 per cent and 1 per billion.

Conclusions: The evaluation of the published materials supports the hypothesis that - although familial clustering of MM is largely attributable to shared asbestos exposure - the additional contribution of factors dealing with genetic susceptibility may play a role in the etiology of MM.

In plain English

This article was a mini review of published reports of malignant mesothelioma (MM) in more than one member of the same family. A PubMed search found 82 citations, 20 of which reported a family cluster, and three more articles were found through reference lists. The review also discussed the Cappadocia epidemic, linked to the mineral fiber erionite, and studies of cancer in relatives of MM patients. The authors applied a statistical test, the Family History Score, to six family clusters with 3 to 5 MM cases each, assuming every family member was exposed to asbestos. Scores ranged from 1.70 to 2.81 assuming a 17% lifetime risk and from 3.04 to 4.11 assuming a 10% lifetime risk. Chance alone was rejected for all families except one under the 17% assumption. Unpublished data from the authors' institute (Andreatta et al.) compared 115 pleural MM patients with 198 controls. Those data found more colon cancer among the patients' first-degree relatives (adjusted OR 2.4, 95% CI 1.2–4.7). The authors concluded that asbestos exposure appears to be a prerequisite, but that an inherited susceptibility is likely also involved.

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: Mini review (literature review) of published familial clusters of mesothelioma, with a statistical test (Family History Score) applied to selected published clusters
• Who was studied: Published reports of familial mesothelioma found through PubMed without language or time restriction: 82 citations retrieved, 20 reporting a familial cluster, plus 3 found through references. The Family History Score was applied to 6 family clusters with 3 to 5 MM cases each.
• Exposure: Shared occupational, domestic or environmental asbestos exposure among family members, which was uncertain or absent in some reports. For the Family History Score, all family members were assumed to be asbestos-exposed, with a lifetime MM risk of 10% (exposed) or 17% (heavily exposed).
• Main results:
  • Six familial clusters, each with 3 to 5 MM cases, could be evaluated with the Family History Score.
  • The family scores for the six clusters ranged from 1.70 to 2.81 assuming a 17% lifetime risk, and from 3.04 to 4.11 assuming a 10% lifetime risk.
  • Random occurrence of the clusters was rejected in all families except one when a 17% lifetime risk was assumed, with a first type error between 1 per cent and 1 per billion depending on the assumed lifetime risk. A Bonferroni correction for multiple testing was applied.
  • In unpublished data from the authors' institute (Andreatta et al.), 115 pleural MM patients were compared with 198 matched controls. Colon cancer was more common among the patients' first-degree relatives, and this held after adjusting for sex, age, occupation and asbestos exposure (OR 2.4, 95% CI 1.2–4.7).
  • In the same unpublished data, none of the nine patients with relatives affected by colon cancer reported familial asbestos exposure.
• The authors' conclusion: The authors concluded that asbestos exposure appears to be a prerequisite for MM. They wrote that shared exposure does not fully explain the familial pattern and that an inherited susceptibility is likely involved. In their view this is probably polygenic rather than a strong single-gene factor.
• Limitations the authors state:
  • The quality of the available information in the published literature is generally poor.
  • Reporting or publication bias may exist and could not be addressed in the review.
  • Other environmental exposures shared within families, such as diet, air pollution or viruses, could affect the response to asbestos.
  • Because MM is rare, it is very difficult to estimate the weight of inherited susceptibility by comparing blood relatives with non-blood-related family members.
  • The role of chance in the familial clusters cannot be completely ruled out.
  • Recall bias must be considered in the studies of family history of cancer.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Etiology, Carcinogenic, Mineral Fiber, Mesothelioma, Asbestos Exposure.

Related studies

• Genetic susceptibility to malignant pleural mesothelioma and other asbestos-associated diseases — M. Neri, D. Ugolini, et al. (2008)
• Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure — M. Neri, R. Filiberti, et al. (2005)
• Pooled analysis of NAT2 genotypes as risk factors for asbestos-related malignant mesothelioma — M. Betti, M. Neri, et al. (2009)
• Genetic susceptibility to asbestos-related fibrotic pleuropulmonary changes — M.K. Kukkonen, S. Hämäläinen, et al. (2011)
• Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study — G. Matullo, S. Guarrera, et al. (2013)
• Genetic predisposition for malignant mesothelioma: A concise review — M. Betti, A. Aspesi, et al. (2019)

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