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Genetic Risk Factors for Mesothelioma
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Genetic testing for mesothelioma is key for early detection, treatment and survival. Research suggests genetic risk factors, such as a mutated BAP1 gene, increase the likelihood an individual will develop mesothelioma as a result of asbestos exposure.
Written by Karen Selby, RN | Medically Reviewed By Dr. Jeffrey Velotta | Edited By Walter Pacheco | Last Update: November 20, 2024
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Written by Karen Selby, RN | Medically Reviewed By Dr. Jeffrey Velotta | Edited By Walter Pacheco | Last Update: November 20, 2024
How Does Genetics Impact Mesothelioma Risk?
Research shows that some genes might raise the risk of mesothelioma after asbestos exposure. The risk also depends on how much and how long someone is exposed to asbestos. Some genes might explain why some people are more prone to diseases from asbestos
Mesothelioma can occur in people after minimal exposure to asbestos. The most well-known mesothelioma genetic risk factor is BAP1, a tumor-suppressor gene. Several studies show a BAP1 mutation is a risk factor for mesothelioma.
About 12% of mesothelioma cases develop in people with mutations of BAP1 or other genes. Prevention is crucial for those at risk.
BAP1 Gene and Mesothelioma
In 2007, scientists studied families in an area of Turkey known for asbestos exposure. They found that a BAP1 gene mutation increases the risk of mesothelioma.
After several years of studying a unique mesothelioma epidemic in Cappadocia, Turkey, we noted that in certain families, up to 50% of family members developed mesothelioma. We demonstrated that susceptibility to mesothelioma was transmitted genetically from one generation to the next.
Dr. Michele Carbone, Director of thoracic oncology at the University of Hawaii Cancer Center
Another study evaluated two U.S. families with high incidences of mesothelioma. Researchers found a BAP1 mutation in every family member with mesothelioma. Additional research has also linked this gene to mesothelioma..
Is Mesothelioma Hereditary?
Mesothelioma is not hereditary. However, some people inherit genes that raise their risk after asbestos exposure. For instance, those with a mutated BAP1 gene face a higher risk if exposed to asbestos, the main cause of mesothelioma.
Quick Fact
Chromosomes contain protein and DNA and the BAP1 gene is found on chromosome three. People inherit a mutated version of this gene from one or both of their parents.
The BAP1 gene controls calcium in cells. If it’s damaged or mutated, calcium levels fall. This raises cancer risk from substances like asbestos. For those with a BAP1 mutation, asbestos exposure raises mesothelioma risk.
Using Genetics to Treat Mesothelioma
Some researchers believe that fixing genetic mutations may help prevent and treat mesothelioma. For example, a 2017 Nature study found that a normal BAP1 gene and repaired calcium channels led to positive chemotherapy results.
You cannot fix something unless you know what is broken. We discovered the first, and so far, only known biological mechanism that makes some people more susceptible. The fixed channels should be able to prevent cancer in people who have inherited the mutation. It can also help treat cancers whose tumor cells have developed mutations.
Dr. Michele Carbone, Director of thoracic oncology at the University of Hawaii Cancer Center
A clinical trial set to wrap up in 2026 is testing a drug called TAK-500 that targets immune system genes. The hope is that the drug will stimulate the immune system to attack mesothelioma.
In 2018, a clinical trial tested the immunotherapy drug olaparib, or Lynparza. Researchers aimed to see how well it worked for pleural and peritoneal mesothelioma.
Lynparza is a protein inhibitor effective against breast and ovarian cancers. It targets the BRCA gene, a close relative to BAP1. Researchers hoped for similar results in mesothelioma, but it proved ineffective.
How Genetics Impact Prognosis
Doctors have a hard time predicting how long mesothelioma patients will live. Genetic testing may improve estimates of how long someone may survive with mesothelioma.
A 2022 research study noted that DNA could show a patient’s resistance to chemotherapy drugs. Another 2022 study looked at the effects of BAP1 status on survival. About 60% of participants had BAP1 loss. In those patients, median survival after chemo was longer by almost 13 months.
The Proceedings of the National Academy of Sciences looked at mesothelioma in 2019. They studied how DNA repair genes impact mesothelioma survival. Patients with a DNA suppressor gene mutation survived longer than those without.
Impact of DNA Suppressor Gene Mutation on Mesothelioma Patient Survival
| With Mutation | Without Mutation |
|---|---|
| 7.9-year median survival | 2.4-year median survival |
Source:
Proceedings of the National Academy of Sciences, 2019
BAP1 increases the risk of developing mesothelioma but also improves long-term survival. Research shows they respond better than the average patient. This might mean people with this mutation could get more aggressive treatment.
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Find a Clinical TrialOther Genetic Biomarkers of Mesothelioma
Ongoing studies continue to explore the link between gene mutations and cancer. Researchers hope to learn more about what causes tumors to grow and mutate.
Some drugs and treatments can prevent genetic mutations and treat cancer. Gene therapy is a field of medicine that aims to repair genes to prevent and treat tumors.
Gene therapy uses portions of healthy DNA (1) to replace damaged genes in the body. Inactive viruses (2) carry the healthy gene segments to damaged cells and make copies (3) that target cancer.
Researchers in Belgium studied a family with a history of mesothelioma in 2014. Investigators ruled out BAP1 as a cause of mesothelioma in this family. They identified 11 other possible gene mutations.
The most prominent mutation was RBM15. The study could not prove these mutations caused mesothelioma or other cancers.
Many mutations correlate with other cancers. Gaining a better understanding of these mutations helps researchers personalize treatment further. Several drugs that target those mutations already exist.
This Page Contains 12 Cited Articles
The sources on all content featured in The Mesothelioma Center at Asbestos.com include medical and scientific studies, peer-reviewed studies and other research documents from reputable organizations.
- Carbone, M., Minaai, M., Takinishi, Y., Pagano, I., & Yang, H. (2023). Preventive and therapeutic opportunities: targeting BAP1 and/or HMGB1 pathways to diminish the burden of mesothelioma. Retrieved from https://doi.org/10.1186/s12967-023-04614-5
- Louw, A. et al. (2022, July). BAP1 Loss by Immunohistochemistry Predicts Improved Survival to First-Line Platinum and Pemetrexed Chemotherapy for Patients With Pleural Mesothelioma: A Validation Study. Retrieved from https://pubmed.ncbi.nlm.nih.gov/35489694/
- Bronte, G., Procopio, A.D. & Graciotti, L. (2022, June). The application of cancer stem cell model in malignant mesothelioma. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S1040842822001226
- National Cancer Institute. (2021). Asbestos Exposure and Cancer Risk. Retrieved from https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/asbestos/asbestos-fact-sheet
- U.S. National Library of Medicine. (2019, May 2). A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001). Retrieved from https://clinicaltrials.gov/ct2/show/NCT03207347?term=nct03207347&rank=1
- Hassan, R. et al. (2019, April 30). Inherited predisposition to malignant mesothelioma and overall survival following platinum chemotherapy. Retrieved from https://www.pnas.org/content/116/18/9008.abstract
- U.S. National Library of Medicine. (2019, March 21). Long Term Follow-up of Mesothelioma Patients and Their Family Members With Germline Mutations in BAP1 and Other Genes. Retrieved from https://clinicaltrials.gov/ct2/show/NCT03830229?term=NCT03830229&rank=1
- Hylebos, M. et al. (2018, June 30). Molecular analysis of an asbestos-exposed Belgian family with a high prevalence of mesothelioma. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29961174
- U.S. National Library of Medicine. (2018, June 19). Olaparib in People With Malignant Mesothelioma. Retrieved from https://www.clinicaltrials.gov/ct2/show/NCT03531840
- Barbiero, F. et al. (2018, June 5). Cancer incidence in a cohort of asbestos-exposed workers undergoing health surveillance. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29869702
- Clinical Trials. (2024, August). A Study of TAK-500 With or Without Pembrolizumab in Adults With Select Locally Advanced or Metastatic Solid Tumors. Retrieved from https://clinicaltrials.gov/study/NCT05070247
- Ghafoor, A. et al. (2021). Phase 2 Study of Olaparib in Malignant Mesothelioma and Correlation of Efficacy With Germline or Somatic Mutations in BAP1 Gene. Retrieved from https://pubmed.ncbi.nlm.nih.gov/34661178/
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