In serving as a peer reviewer of legal publications, I have encountered authors who assert in manuscripts that all human mesotheliomas are caused by asbestos. This assertion was false back in the 1980s when I was trying mesothelioma cases, but today the assertion is demonstrably false. The lawsuit industry and its expert witnesses have propagated the assertion relentlessly for the last four decades, and their over-zealous advocacy has distorted the discussion of causal claims in legal venues. When I have encountered these statements in manuscripts, I have suggested more accurate and felicitous descriptions, which only sometimes were adopted.
Scientists have long suspected that there were genetic determinants, and indeed causes, of human mesothelioma. Establishing this suspicion as fact has proven difficult in part because of the difficulty in conducting full genome sequencing of large numbers of mesothelioma patients. For some time, scientists have been publishing studies, however, which have undermined the dogma of the lawsuit industry. Last month, an important study was peer-reviewed and published in Science Reports, a journal in the Nature family, which further chipped away at the dogma, by showing the importance of certain BAP1 mutations in the rate of spontaneous malignant mesothelioma, in in-bred mice without asbestos exposure. The article is open access, and should be on the reading list of practicing lawyers and commentators who concern themselves with asbestos, and the issue of supposed pathognomonic diseases in the courts.[1] The medico-legal implications of the publication are obvious. Mesothelioma can result from highly penetrant genetic mutations in the absence of any asbestos exposure. I have reproduced the authors’ abstract below, but interested readers should obtain and study the entire study.
“Cancers of the mesothelium, such as malignant mesothelioma (MM), historically have been attributed solely to exposure to asbestos. Recent large scale genetic and genomic functional studies now show that approximately 20% of all human mesotheliomas are causally linked to highly penetrant inherited (germline) pathogenic mutations in numerous cancer related genes. The rarity of these mutations in humans makes it difficult to perform statistically conclusive genetic studies to understand their biological effects. This has created a disconnect between functional and epidemiological studies. However, since the molecular pathogenesis of MM in mice accurately recapitulates that of human disease, this disconnect between functional and epidemiological studies can be overcome by using inbred mouse strains that harbor mutation(s) in genes involved in the disease. Most mouse studies have focused on the effect of asbestos exposure, leaving the effects of genetic mutations in the absence of exposure understudied. Here, using existing peer-reviewed studies, we investigate the rate of spontaneous MM among mice with and without germline genetic mutations, in the absence of asbestos exposure. We leveraged these published data to generate a historical control dataset (HCD) to allow us to improve statistical power and account for genetic heterogeneity between studies. Our Bayesian analyses indicate that the odds of spontaneous MM among germline BAP1 mutant mice is substantially larger than that of wildtype mice. These results support the existing biological study findings that mesotheliomas can arise in the presence of pathogenic germline mutations, independently of asbestos exposure.”
[1] Dahlia M. Nielsen, Mei Hsu, Michael Zapata III, Giovanni Ciavarra & Leonel van Zyl, “Bayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposure,” 15 Sci. Reports 169 (2025).
