The primary question in many toxic tort cases is what caused the disease? When defending these cases, one necessarily asks: (1) is the product/substance I am defending capable of causing the disease in question; and (2) was the plaintiff exposed to enough of it to have done so.

With cases involving cancer, particularly mesothelioma, genetic science is adding to the mix and providing information that, in the right case, changes the equation entirely.

Generally, cancer is a genetic disease caused by gene mutations that control how cells grow and multiply (NIH The Genetics of Cancer, 2022). While cells are the bodys building blocks, genes are sections of DNA in each cell that provide instructions to make required proteins and control cell growth. Hundreds of DNA and genetic changes (variants, mutations or alterations) have been discovered that help cancer form, grow and spread.

My experience with these issues arises from the defense of asbestos cases. The principles raised, however, may well apply to other toxic torts involving cancer.

It is now recognized that there are multiple causes for malignant mesothelioma, a number of which are unrelated to asbestos. Diffuse malignant mesotheliomas are variably associated with prior asbestos exposure, and the strength of the association varies with anatomical tumor site, gender and asbestos fiber type.

The relationship between asbestos and mesothelioma has also evolved and shows significant geographic variation. The epidemiological evidence correlating time trends, incidence by gender, and commercial asbestos use indicates that a majority of pleural mesotheliomas in women, and almost all peritoneal mesotheliomas in women and men, in the United States, appear unrelated to asbestos.

In July 2019, many of the worlds foremost experts on the subject detailed the current state-of-the-art knowledge on the development of mesothelioma. See Carbone, et al., Mesothelioma: Scientific Clues for Prevention, Diagnosis, and Therapy, CA Cancer J Clin., 69:402-429 (2019).

Among the co-authors of the publication were preeminent researchers and practitioners from the University of Hawaii Cancer Center, Memorial Sloan Kettering Cancer Center, Rutgers Robert Wood Johnson Medical School, Brigham and Womens Hospital, Mayo Clinic, Icahn School of Medicine at Mount Sinai, and MD Anderson Cancer Center. Under a section of the publication entitled The Role of Genetics, the authors state:

When examining a toxic tort/cancer case, it may not always be the environment or the toxin that is the culprit. If a plaintiff has an appropriate family history of cancer, genetic testing may provide a viable defense.

Cancer is caused by the accumulation of genetic damage. Genetic damage can be inherited, can develop spontaneously, can be caused by exposure to carcinogens and oncogenic infectious agents, or can be caused by the interplay of a combination of these factors. Currently, there is a very active debate about the relative contribution of these factors to human cancer . [A] growing percentage of cancers are attributed to inherited mutations of DNA repair genes and of other genes that, when mutated, accelerate the accumulation of DNA damage and/or the percentage of cells carrying DNA damage . These concepts apply to mesothelioma.

In broad strokes, there are two types of genetic cases: (1) cases involving somatic or random genetic mutations; and (2) cases involving a germline genetic mutation.

Somatic random mutations develop because of DNA changes that occur during stem cell divisions. These mutations arise naturally and accumulate as a person ages. Age is a significant risk factor for almost all forms of cancer, including spontaneous or naturally occurring mesothelioma.

The basis for age-induced tumorigenesis relates to the hosts generation of critical driver mutations within cells and the subsequent formation of clonally expanded proliferation of mutated cells to form tumors. Stem cell division occurs continuously and requires a faithful replication of the highly complex genetic information contained within the genome and cell nucleus.

Random mistakes or mutations (replication errors) occur continuously and with increasing frequency over time, with the capacity of the host to efficiently identify and correct such mutations diminishing with age.

Because mutation accumulation occurs spontaneously and continuously over time, the risk of spontaneous or naturally occurring mesothelioma, either pleural or peritoneal, increases continuously with age.

Random mutations account for two-thirds of the risk of getting many types of cancer. In such cases, no exposure to an exogenous agent (such as asbestos or therapeutic radiation) is required for tumor initiation. Replicative mutations can be responsible for either initiating the process or driving tumor progression.

The current best available scientific evidence is that some mesotheliomas are linked to inherited germline mutations. Overall, at least 12 percent of mesotheliomas occur in carriers of germline genetic mutations. These germline genetic-induced mesotheliomas typically occur in persons of younger age and are often peritoneal rather than pleural mesotheliomas.

As the cohorts of asbestos workers vanish due to old age, increasing percentages of mesotheliomas, especially peritoneal mesotheliomas, occur in individuals who are not occupationally exposed to asbestos. These mesotheliomas may be caused by environmental exposure, genetic predisposition or both.

Pathogenic germline mutations of BAP1 and, less frequently, of other tumor suppressor genes have also been detected in approximately 12 percent of patients. This subgroup of genetically linked mesotheliomas occurs in younger individuals who rarely report asbestos exposure, and with a M:F ratio of 1:1 and survival ranging from five to 10 or more years.

While heritable gene mutations can predispose an individual to cancer (i.e., lower the amount of exposure necessary to cause disease), they can also be sufficient to cause cancers, including mesothelioma, in and of themselves.

Put another way, the presence of a heritable germline mutation, absent or independent of extrinsic factors such as asbestos exposure, can be a cause of mesothelioma.

While the import of these findings may be largely self-evident, there are some takeaways worth considering. First, when examining a toxic tort/cancer case, it may not always be the environment or the toxin that is the culprit. If a plaintiff has an appropriate family history of cancer, genetic testing may provide a viable defense.

Second, genetic germline mutations do not automatically turn a plaintiff into an eggshell plaintiff. While that argument may work in some cases, given that the mutation can be independently causative, it should not apply in all of them.

Anthony J. Sbarra is a shareholder at Segal McCambridge in Boston and focuses his practice on product liability and toxic tort cases.

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Significance of genetic mutations in toxic tort cases - Massachusetts Lawyers Weekly