The biggest risk factor for developing mesothelioma is exposure to asbestos. But clinical research suggests that people who have a mutated BAP1 gene are more likely to develop asbestos cancer after exposure to the toxin.
How Genetics Affect Mesothelioma Incidence
One of the most challenging questions facing clinical researchers is why some people exposed to asbestos get cancer but most do not. It is true that exposure levels and length of exposure play significant roles, and researchers have determined that some people are more susceptible to the negative effects of toxic asbestos.
For instance, cases of mesothelioma have been found in people who were only exposed to asbestos once. In such cases, researchers think there were genetic factors that made the person more prone to getting cancer. But there are many cases where people were exposed to asbestos for years and never got mesothelioma.
The most-publicized genetic risk factor is the tumor-suppressor gene BAP1. Several clinical trials show that mutations of this gene boost the chances of getting mesothelioma, especially after asbestos exposure.
Understanding the link between genetic risk factors of this cancer will help scientists to develop ways to prevent disease. More effective treatment options could be made possible, too.
BAP1 Gene and Mesothelioma
A 2011 clinical study done at the University of Hawaii Cancer Center and Fox Chase Cancer Center in Philadelphia found people who have a mutation in the BAP1 gene are more likely to get mesothelioma.
This gene is located on the short arm of the third chromosome. The study looked at two families in the United States with high rates of mesothelioma and mutation of the gene. Researchers found that every member of the family who was diagnosed with mesothelioma had the BAP1 mutation.
Additional research showed that the BAP1 mutation exists in 70% of people with mesothelioma. This makes the gene a target to prevent the disease, as well as to detect and treat it early. Only 20% of other cancers are related to the presence of the BAP1 mutation.
The BAP1 gene regulates a process that puts calcium inside cells. When the gene is mutated or damaged, calcium levels are reduced. This makes it more likely that mesothelioma can develop when the person is exposed to asbestos.
Can You Inherit Mesothelioma?
Research shows that exposure to asbestos is the top cause of mesothelioma. But a person can be born with the defective BAP1 gene, and this is often inherited. The BAP1 mutation also may develop later in one’s life as cells develop a malignancy.
Using BAP1 Gene For Screening
The National Cancer Institute started a clinical trial in early 2019 to explore people who are more likely to be diagnosed with mesothelioma, and possible solutions to deal with it. The NCI is studying the BAP1 gene and other similar genes in this trial.
NCI senior investigator Raffit Hassan, MD, thinks the study could bring about a screening process and regular examinations for people who have those genetic mutations.
Hassan noted this is a vital long-term study that could have serious implications for the patient and family members. Progress is possible because there could be prevention and/or early detection of mesothelioma.
If the mutation is not found in a person who has asbestosis, for instance, it can reduce the fear of the person that he may get mesothelioma or other cancers. If doctors do find the BAP1 mutation, they can offer the patient options to reduce the chances of getting cancer, such as not working in places where asbestos is present.
Testing for the gene means a blood sample must be taken. It takes about two weeks for results to come back. A positive test result means the gene is a mutation and a negative result means the gene is not mutated and is normal.
Genetics and Treating Mesothelioma
A June 2017 study in Nature magazine explains why someone with the BAP1 mutation becomes more resistant to cancer treatments, such as chemotherapy. Researchers discovered that mesothelioma cells are more responsive to chemotherapy when the levels of BAP1 are normal and calcium channels are repaired and made stable. (Nature.com)
The fixed channels may be able to prevent mesothelioma in patients who have the genetic mutation. It also can help treat cancers with tumor cells that have mutations, according to Michele Carbone, MD, director of thoracic oncology at the University of Hawaii Cancer Center.
Genetics and Prognosis
It is hard for physicians to predict how long a particular mesothelioma patient will live. In future years, genetic testing might be used to give us more accurate estimates of how long a person can live with asbestos cancer.
A 2019 study released in the Proceedings of the National Academy of Sciences (PNAS.org) revealed how genetic mutations of DNA repair genes may affect mesothelioma survival times. Patients with a mutation of a DNA suppressor gene lived longer than those who did not have the mutation. The study found that if the patient had the mutation, they lived a median of 7.9 years from diagnosis. Without it, they lived a median of only 2.4 years.
It looks as if BAP1 heightens the risk of getting mesothelioma. But it can improve the chances of living longer. In the future, this might mean people with the gene can get more aggressive treatment because clinical research shows they respond better than other patients.
Searching for Other Genetic Biomarkers To Detect Mesothelioma Early
Clinical studies continue to look for a connection between mesothelioma and gene mutations. Researchers hope to find more about what causes mesothelioma tumors to grow, how to prevent mutations, and which treatments and drugs can prevent the spread of the disease.
Belgian researchers have studied a family who has a strong history of asbestos cancer. Clinical investigators ruled out BAP1 as the cause in this family in 2014, but it found 11 other potential gene mutations that could be the cause. The most promising one was RBM15. But this study could not prove that gene mutation caused mesothelioma in the family. (asbestos.com)
More research is needed, but findings have been promising in the study of the possible genetic reasons that people are more likely than others to develop mesothelioma.
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