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Genetic Risk Factors for Mesothelioma
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Genetic testing for mesothelioma may be important for early cancer detection, treatment and survival rate. 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: June 27, 2024
Written by Karen Selby, RN | Medically Reviewed By Dr. Jeffrey Velotta | Edited By Walter Pacheco | Last Update: June 27, 2024
How Does Genetics Impact Mesothelioma Risk?
Research suggests certain genes may increase the risk of mesothelioma after asbestos exposure. The amount and duration of asbestos exposure play significant roles in whether someone develops mesothelioma. Specific genes may explain why some people are more susceptible to asbestos-related diseases.
12%
Percentage of mesothelioma cases that develop in people with mutations of BAP1 or other genes.
Mesothelioma cases can occur in people after a single 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. For people with genetic risk factors, prevention techniques are essential.
BAP1 Gene and Mesothelioma
In 2007, scientists studied the risk of mesothelioma among certain families within a region of Turkey known for asbestos exposure. They discovered people with a BAP1 gene mutation are susceptible to developing 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.
Another study evaluated two U.S. families with high incidences of mesothelioma. Researchers noticed every family member with mesothelioma also carried the BAP1 mutation. Further research has supported a connection between the gene and mesothelioma.
Is Mesothelioma Hereditary?
Mesothelioma is not hereditary. Some people inherit genes that increase the risk of mesothelioma following asbestos exposure. A person born with a mutated BAP1 gene has a higher risk of mesothelioma if they are exposed to asbestos, which is the leading 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 regulates a channel that moves calcium inside cells. With gene damage or mutation, calcium levels drop. As this happens, cancer risk is higher from carcinogens like asbestos. Asbestos exposure increases mesothelioma risk in someone with a BAP1 gene mutation.
Using Genetics to Treat Mesothelioma
Researchers have theorized 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 CarboneDirector of thoracic oncology at the University of Hawaii Cancer Center
A 2018 clinical trial studied the immunotherapy drug olaparib (Lynparza). Researchers examined its response rate in 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 hope for similar results in mesothelioma.
How Genetics Impact Prognosis
It is difficult for doctors to predict mesothelioma patient life expectancy. 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.
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 receive more aggressive treatment.
A 2022 research 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.
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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 allows researchers to personalize treatment further. Several drugs that target those mutations already exist.
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