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Updated: Jan 20, 2026
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Genetic predisposition for malignant mesothelioma: A concise review
Marta Betti1, Anna Aspesi1, Marika Sculco1
1Department of Health Sciences, Università del Piemonte Orientale, via Solaroli 17, 28100 Novara, Italy.
Abstract:
Malignant mesothelioma (MM) is an aggressive cancer associated with asbestos exposure. Studies of familial malignant pleural mesothelioma (MPM) have suggested the existence of a genetic predisposition. Information on the role of genetic risk factors in the development of MM has been growing in the last years, and both low- and high-risk genetic factors have been identified, but genetic factors alone (without any exposure to asbestos or other mineral fibers) have never been shown to induce MM. Low-risk genetic factors have been identified in studies that systematically analyzed the whole genome. When considered alone these low-risk genetic factors carry a relative risk of MPM that is 10- to 15-fold lower than that carried by asbestos exposure; however, a large number of these factors in combination may increase the impact of asbestos exposure. High-risk genetic factors include truncating variants in the tumor suppressor BAP1 and in other tumor suppressor genes belonging to DNA repair pathways. Heterozygous germline variants in these genes may favor carcinogenesis if a second somatic variant occurs that impairs the wild-type allele. This impairment can cause genetic instability due to the suppression of a specific DNA repair pathway, and transformation. This genetic predisposition may have translational consequences, as it may predict patient response to drugs that induce tumor-specific synthetic lethality.
Insights
Genetic factors influence malignant mesothelioma (MM) risk, with high-risk variants like BAP1 mutations increasing susceptibility. Combined genetic factors and asbestos exposure elevate MM risk, impacting treatment strategies.
Area of Science:
- Oncology
- Genetics
- Environmental Health
Background:
- Malignant mesothelioma (MM) is an aggressive cancer strongly linked to asbestos exposure.
- Familial studies suggest a genetic predisposition to malignant pleural mesothelioma (MPM).
- Growing evidence identifies both low- and high-risk genetic factors in MM development.
Purpose of the Study:
- To explore the role of genetic risk factors in malignant mesothelioma development.
- To understand how genetic predisposition interacts with environmental exposures like asbestos.
- To investigate the translational implications of genetic findings for patient treatment.
Main Methods:
- Genome-wide association studies (GWAS) to identify low-risk genetic factors.
- Analysis of high-risk genetic factors, including variants in tumor suppressor genes (e.g., BAP1) and DNA repair pathways.
- Investigation of germline variants and their interaction with somatic mutations in carcinogenesis.
Main Results:
- Low-risk genetic factors, individually, confer a significantly lower relative risk of MPM compared to asbestos exposure.
- Combinations of low-risk genetic factors may amplify the risk associated with asbestos exposure.
- High-risk genetic factors, such as BAP1 truncating variants, predispose individuals to cancer when a second hit occurs, leading to genetic instability.
Conclusions:
- Genetic predisposition plays a role in MM development, often in conjunction with asbestos exposure.
- Germline variants in tumor suppressor and DNA repair genes can increase cancer risk through loss of heterozygosity and subsequent genetic instability.
- Understanding genetic risk factors may enable personalized medicine approaches, predicting patient response to specific therapies like synthetic lethality drugs.
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