BAP1 as Independent Cause

Recent reviews of genetic research continue to challenge long-held assumptions about the causes of malignant mesothelioma. While plaintiffs’ attorneys often cite to asbestos exposure as the only cause of mesothelioma, a January 2025 publication in Scientific Reports led by Dahlia Nielsen includes a novel approach to the subject and provides further evidence that certain inherited genetic mutations—most notably in the BAP1 gene—can independently cause mesothelioma, even in the absence of asbestos exposure.¹ The results of Nielsen’s Bayesian analysis and findings, together with a brand new paper² by Dr. Michele Carbone’s group (which may find its way into a future blog), may alter the landscape of asbestos litigation and influence the strategies used by both plaintiffs and defendants.

A Paradigm Shift: Genetic Causation

Asbestos exposure has long been considered the primary cause of mesothelioma, influencing the course of thousands of lawsuits. However, an ever-increasing body of literature supports the thesis that BAP1 and other genetic mutations are capable of causing mesothelioma absent asbestos exposure. The Nielsen study employs a Bayesian analysis to review the research challenging this perspective. Nielsen and her co-authors conclude that their analyses indicate the odds of spontaneous malignant mesothelioma among germline BAP1 mutant mice is substantially larger than that of wildtype mice. Nielsen et al. argue this conclusion demonstrates that mutations in the BAP1 gene can independently trigger mesothelioma.³

In the Nielsen study, researchers reviewed previous studies and incorporated additional comparative data, finding a 96.7% to 99.5% probability that BAP1 gene mutations alone can greatly increase the risk of a spontaneous mesothelioma among BAP1 mutant mice as compared to the increased risk among wildtype mice, even without asbestos exposure.  By pooling data from thousands of unexposed mice (both BAP1 mutant and wildtype) in published data from prior studies, Nielson’s analyses showed that mice with BAP1 mutations developed spontaneous mesothelioma at dramatically higher rates compared to controls. In fact, their analyses show the  odds of developing mesothelioma were over 20 times higher in BAP1 mutant mice, providing robust evidence that inherited genetic factors—especially BAP1 mutations—can be a sole cause of mesothelioma. According to Nielsen, some of these studies now suggest that inherited mutations in highly penetrant cancer-related genes like BAP1 may account for 20–36% of all mesothelioma  cases.

Legal Precedents and the Evolving Role of Genetic Evidence

While genetic causation evidence has been accepted in other types of toxic tort litigation, its use in mesothelioma litigation has lagged. This may be attributable to an undersupply of peer-reviewed studies regarding the effects of genetic mutations in the absence of asbestos exposure. The Nielsen study (and the latest Carbone paper) help fill a critical void in the literature by utilizing a Bayesian analysis to examine the criteria that have previously been understudied, remedying a longstanding deficiency in the available data.  As motions for genetic testing are heavily contested by plaintiffs, and courts are still reluctant to permit testing in all but the clearest of cases, , the Nielsen study provides an additional analysis of current scientific data to combat arguments that genetic abnormalities alone cannot cause mesothelioma—a position that may become increasingly difficult to maintain as scientific evidence and the analyses of that evidence continue to develop.

With Nielsen’s novel approach to the existing science, defendants now have a powerful tool to challenge the assertion that asbestos is or was the sole cause of a plaintiff’s illness. For plaintiffs, understanding the latest genetic science—and how genetic testing might impact their case—is now more important than ever.

A New Era in Mesothelioma Litigation

The Nielsen study and related genetic research mark a new understanding of mesothelioma causation. As courts and litigants grapple with more scientific advances, the focus of asbestos litigation is shifting from external exposures to an analysis of the complex interplay connecting environmental and genetic factors. The increasing recognition that inherited germline mutations, especially in BAP1, can independently cause mesothelioma – absent asbestos exposure – marks a significant shift in both science and law.

1. Nielsen, D.M., Hsu, M., Zapata, M., et al., Bayesian analysis of the rate of spontaneous MM among BAP1 mutant mice in the absence of asbestos exposure, Sci Rep 15, 169 (2025), https://doi.org/10.1038/s41598-024-84069-w. ↩︎
2. Carbone M, Minaai M, Kittaneh M, Krausz T, Miettinen MM, Hammarström QP, Hammarström L, Abolhassani H, Pagano I, Xu R, Novelli F, Gaudino G, Pastorino S, Sarin KY, Ripley RT, Pass HI, Schrump DS, Yang H, Clinical and Pathologic Phenotyping of mesotheliomas developing in carriers of Germline BAP1 Mutations, Journal of Thoracic Oncology (2025), doi: https://doi.org/10.1016/j.jtho.2025.06.020. ↩︎
3. Testa, J.R., Cheung, M., Pei, J., et al., Germline BAP1 mutations predispose to malignant mesothelioma, Nat. Genet. 2011, 43(10):1022-1025; Cheung, M., Kadariya, Y., Sementino, E., et al., Novel LRRK2 mutations and other rare, non-BAP1-related candidate tumor predisposition gene variants in high-risk cancer families with mesothelioma and other tumors, Hum. Mol. Genet. 2021, 30(18):1750-1761. ↩︎