Researchers have shown that even minimal exposure to chrysotile asbestos may increase susceptibility to the development of malignant mesothelioma in mice with BAP1 germline mutations, according to new findings presented by Kadariya et al at the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract 1468/6) and simultaneously published in Cancer Research Communications.
Background
Patients with BAP1 mutations may have an increased risk of developing certain tumors occurring in the abdomen, skin, eyes, kidneys, and tissue lining the chest. Notably, these patients have an increased risk of malignant mesothelioma, which occurs when cancer cells form in the mesothelium.
“There is a specific type of asbestos called chrysotile, and it’s often debated whether it can or can’t cause mesothelioma or lung cancer. This new study is particularly relevant given that chrysotile currently makes up approximately 95% of asbestos used commercially. While some say it causes these diseases, others say if it does, it is only because it is contaminated with another type of asbestos called crocidolite,” explained senior study author Joseph Testa, PhD, FACMG, the Carol & Kenneth E. Weg Chair in Human Genetics and Chief of Genomic Medicine at Fox Chase Cancer Center.
Study Methods and Results
In the preclinical study, the researchers used low level injections of chrysotile and crocidolite asbestos to examine the incidence of mesothelioma in mice with BAP1 mutations and mice with normal genomes. They found that regardless of the level of asbestos exposure, the mice with BAP1 mutations developed mesothelioma more often than those without the mutations.
The researchers also discovered that inflammation triggered by exposure to asbestos, especially chrysotile, resulted in an immunosuppressive tumor microenvironment in the mice with BAP1 mutations mice—creating conditions that allowed malignant mesothelioma cells to evade immune surveillance.
Conclusions
The researchers proposed that immunotherapies targeting these pathways in patients with BAP1 mutations who developed malignant mesothelioma may be effective treatment options.
“Drawing parallels to human disease, our experimental findings indicate that BAP1 mutation carriers are highly susceptible to the carcinogenic effects of even minimal amounts of asbestos, including both crocidolite and chrysotile,” emphasized Dr. Testa.
“Because low levels of either form of asbestos caused mesotheliomas in some genetically normal mice, the findings also have relevance to the general public, especially in developing countries where asbestos is unregulated and used without proper precautions,” concluded lead study author Yuwaraj Kadariya, MD, PhD, Assistant Research Professor at Fox Chase Cancer Center.
Disclosure: For full disclosures of the study authors, visit abstractsonline.com and aacrjournals.org.
