Genetic Risk for Mesothelioma

It is well-established that the primary risk factor for developing mesothelioma is exposure to asbestos fibers.

Genetic research that shows a link to those who have a mutated version of the BAP1 gene and an increased risk of mesothelioma development and this risk is magnified if exposed to asbestos. Other biomarkers can be used to gauge risk for mesothelioma and to detect it as early as possible.

How Genetics Impact Mesothelioma Risk and Incidence

One of the most difficult questions to answer in the field of mesothelioma research is why some people develop mesothelioma while other people do not. There are some variables involved regarding exposure levels and exposure duration and those undoubtedly play a role.

Research has demonstrated some people are simply more sensitive to asbestos fibers and are more susceptible to the negative effects.

There are some cases where only a single exposure has resulted in a confirmed diagnosis of mesothelioma. Cases like these are the reason researchers determined there must be other risk factors that can predispose someone to mesothelioma development. It turns out that some of these risk factors are genetic.

BAP1 is currently the most well-known and studied genetic risk factor. The BAP1 gene plays a part in the body’s tumor suppression and there is the possibility that a mutated version can be responsible for increased mesothelioma risk. By continuing to study the links between genetics and mesothelioma, researchers can create more effective prevention and treatment methods.

The BAP1 Gene and Mesothelioma

In 2011 a cooperative study between the University of Hawaii Cancer Center and the Fox Chase Cancer Center in Philadelphia, it was discovered that those who possess the mutated BAP1 gene were much more susceptible to developing mesothelioma. 

The gene is responsible for regulating a channel that provides calcium to cell interiors. If the gene becomes damaged or mutated, the gene’s ability to properly regulate calcium is hindered and calcium levels drop. This creates a high chance of malignancy when exposed to asbestos or other carcinogens.

The BAP1 gene is located on chromosome three, on the short arm. The mutated BAP1 gene is found in approximately 70% of all mesothelioma cases, not only making it a potential biomarker for prevention, but also a gene target for early detection and effective treatment. It is particularly focused on malignant mesothelioma, however, since only about one-fifth of cancers overall are closely associated with the mutated BAP1 vulnerability.

Can Mesothelioma Be Inherited?

Mesothelial cancer has not been observed being passed from mother to child and asbestos exposure is the primary cause of mesothelioma.

A person can, however, be born with a damaged or mutated BAP1 gene that has been inherited. The BAP1 mutation can also occur later in life as cells multiply and become mutated.

Using BAP1 as a Screening Tool

A recent clinical trial at the National Cancer Institute explored possible predisposition to mesothelioma and searched for possible ways to negate or mitigate it. BAP1 and other genes that act similarly are being investigated in the trial.

It is believed that the study may lead to a standard process for screening and lead to people with the identified mutation getting more routine exams. The results of which could have significant implications for the patient as well as their family. Not only can progress be made in prevention, but also early detection. 

For example, if someone has been diagnosed with asbestosis, being screened for the BAP1 mutation can help provide peace of mind. Individuals can also benefit from the screenings if they are in a high-risk occupation, by determining if they are at an increased risk of mesothelioma and other similar cancers. If the screening determines a BAP1 mutation is present, the doctor or other medical staff can provide ways for the patient to minimize their risk of developing mesothelioma, including avoiding any exposure to asbestos through their occupation.

Screening for BAP1 only requires a blood sample and approximately two weeks for the lab results. The test is designed to look for the mutation, so returning a positive result is a confirmation of the mutation and a negative result indicates that the gene is normal. 

The Role of Genetics in Mesothelioma Treatment

A recent study shows why the mutated BAP1 gene becomes resistant to chemotherapy, which is a common issue among malignant mesothelioma patients.

Research indicates that mesothelioma cells become much more responsive to chemotherapy once the normally functioning calcium channels are restored. 

Another study and clinical trial were conducted investigating a drug usually used for immunotherapy and the response rate in patients with pleural or peritoneal malignant mesothelioma. The drug, Lynparza, inhibits proteins and has already been used to effectively fight ovarian and breast cancers. It specifically targets the BRCA gene which is related to the BAP1 gene. The researchers hope to find additional insight into how the relationship between the two genes may allow for similar success in treating mesothelioma as that found in ovarian and breast cancer treatment.

Other Biomarkers Used in Early Detection

Research continues looking for the link between cancer and mutations in the genetic code.

The hope is that researchers can learn more about tumors and what causes them to grow, ways to prevent or mitigate their development, and what treatments may be effective in preventing its spread once developed.

RBM15

Studies in Belgium of a family with a history of mesothelioma pointed researchers to the gene RBM15. They were able to rule out the BAP1 mutation in the family but saw a possible mutation in the RBM15 gene, but were not able to definitively prove a link to mesothelioma.

HMGB1 Proteins

The University of Hawaii Cancer Center is on the leading edge of research into how some blood proteins can be a crucial indicator for early detection of mesothelioma. It was found that high levels of non-acetylated HMGB1 can be found in people with confirmed asbestos exposure, but no cancer diagnosis yet.