The Impact of Genetics on Mesothelioma Development and Treatment

Mesothelioma is a rare type of aggressive cancer that develops in the tissue that lines the outer surface of some of your organs. This type of cancer is usually associated with asbestos exposure and it is mostly fatal. There are treatment options available for mesothelioma, but for most people with mesothelioma, a cure for the cancer is not possible. While the primary risk factor for mesothelioma is known to be asbestos exposure, research has also shown that certain people with a specific gene are more susceptible to developing this type of cancer. Let us look at the role of genetics in the development of mesothelioma and its impact on the treatment of this type of cancer.

Mesothelioma, also known as malignant mesothelioma, is a type of aggressive and rare cancer that develops in the thin layer of tissue that covers the outer surface of many of your internal organs. This lining is known as the mesothelium. Mesothelioma is an aggressive form of cancer and even though there are treatments, for most people with mesothelioma, the cancer often proves to be deadly. ^(1,2)

Mesothelioma is divided into several different types based on what part of the body the cancer is found in. It is most commonly known to attack the tissue surrounding the lungs, known as pleura. This type of mesothelioma is known as pleural mesothelioma. Another type of mesothelioma is known as peritoneal mesothelioma, which attacks the tissue in the abdomen. Other, rarer types of mesothelioma affect the tissue around the heart, known as pericardial mesothelioma, and around the testicles, known as testicular mesothelioma. ^(3,4)

The symptoms of mesothelioma do not become apparent immediately after the development of the cancer. They tend to develop slowly over a period of time and may not become apparent until many decades after the initial exposure to asbestos. Due to this delay in the onset of symptoms, this type of cancer is often not diagnosed till it has already reached an advanced stage. ⁽⁵⁾

The signs and symptoms of mesothelioma tend to differ from person to person and depend on which part of the body the cancer occurs in. For example, in cases of pleural mesothelioma, which affects the lungs, the signs and symptoms may include: ⁽⁶⁾

• Painful coughing
• Chest pain
• Unexplained weight loss
• Fatigue
• Shortness of breath
• Formation of unusual lumps of tissue underneath the skin on your chest

In peritoneal mesothelioma, which affects the tissue in the abdomen, some of the common signs and symptoms may include: ⁽⁷⁾

• Abdominal pain and swelling
• Nausea and vomiting
• Abdominal cramping
• Unexplained weight loss
• Fatigue

Since the other types of mesothelioma are so rare, the signs and symptoms of these forms of the cancer are not very clear. In pericardial mesothelioma, patients can experience symptoms like chest pain and difficulty in breathing. On the other hand, in cases of testicular mesothelioma, patients may first detect a mass or swelling on a testicle. ^(8,9)

While the most common risk factor for developing mesothelioma cancer is exposure to asbestos fibers, studies have shown that some people who have inherited a mutated version of the BAP1 gene are more susceptible to developing this type of cancer, especially upon being exposed to asbestos. ⁽¹⁰⁾

There are certain genetic risk factors that are known to increase the risk of developing mesothelioma in some people after being exposed to asbestos. In such cases, of course, the levels and duration of exposure to asbestos also play a huge role in whether an individual develops mesothelioma or not. Studies have also shown that some people are much more vulnerable to developing any type of asbestos-related disease. ⁽¹¹⁾

In some people, even a one-time exposure to asbestos is enough to develop mesothelioma. This is because of the mesothelioma genetic risk factor of having a mutated BAP1, which is a tumor-suppressor gene. Many studies have shown that a mutation in the BAP1 gene is a significant risk factor for developing mesothelioma. For people who have this type of genetic risk factor, prevention is of utmost importance to keep mesothelioma at bay. ^(12,13)

In 2011, researchers analyzed the effects of gene mutations on the development of mesothelioma. Studies discovered that people who had a mutation in the BAP1 gene were more susceptible to developing mesothelioma even after just a one-time exposure to asbestos. ⁽¹⁴⁾

Chromosomes present in our bodies are used for storing the DNA. The BAP1 gene is stored on the short arm of chromosome number three. The study, published in Nature journal looked at two families in the United States that had high occurrences of mesothelioma. The researchers found that every family member who had mesothelioma also carried the mutated BAP1 gene. More research also showed that the mutation of the BAP1 gene was observed in nearly 70 percent of all mesothelioma cases. Only about 20 percent of the cancers correlated with the BAP1 gene, making this gene a potential target when looking at prevention therapy for mesothelioma. ^(15,16)

The BAP1 gene is responsible for regulating the channel that helps transport calcium inside the cells. When there is damage or mutation to this gene, the calcium levels in the body experience a sudden drop. As this happens, the cancer risk goes up substantially from carcinogens like asbestos. ⁽¹⁷⁾

Due to the link of the BAP1 gene, many people wrongly believe that mesothelioma is a hereditary disease. Mesothelioma cancer is not hereditary, but it is possible to inherit the risk factor of the BAP1 gene. A person who is born with a mutated BAP1 is at a significantly higher risk of developing this type of cancer. At the same time, exposure to asbestos still remains the biggest cause and risk factor for mesothelioma.

This does not mean that you will always inherit the BAP1 mutated gene. The mutation in the BAP1 gene can also occur at a later stage in life as the cells turn cancerous. Asbestos exposure further boosts this risk of mesothelioma in an individual with a mutated BAP1 gene. ⁽¹⁸⁾

Researchers have been studying the BAP1 gene and other similar genes to understand and identify the risk of developing mesothelioma and find potential solutions. If doctors can successfully locate the BAP1 mutation, they will be able to provide certain precautionary steps to at least reduce the risk of developing mesothelioma. For example, avoiding exposure to asbestos at the workplace and cutting down on tobacco use can significantly reduce the incidence of this type of cancer.

Testing for BAP1 is done with a blood test. A positive blood test indicates that you have a mutation of the BAP1 gene, while a negative test means your BAP1 gene is normal. After the blood test is done, it takes around two weeks to get the results.

There are several other studies that are exploring the potential link between gene mutations and the development of cancer like mesothelioma. Through these studies, researchers hope to learn more about what exactly causes cancerous tumors to grow and mutate. They hope to develop medications and treatments that can prevent these mutations and also stop the spread of cancer. Over the years, cancer researchers have made dramatic progress in the genetic diagnosis of mesothelioma, but there is still a long way to go and much more to learn about the exact role of genetics in the development and treatment of cancers like mesothelioma.

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Also Read:

• Mesothelioma: Causes, Who Is At Risk, Types, Symptoms, Diagnosis, Present Treatment, Emerging Treatment
• What is Malignant Pleural Mesothelioma: Causes, Signs, Symptoms
• Malignant Pleural Mesothelioma: Risk Factors, Diagnosis
• Life Expectancy in Malignant Pleural Mesothelioma & its Prognosis and Prevention
• Pericardial Mesothelioma: Causes, Signs, Symptoms, Diagnosis
• What is Peritoneal Mesothelioma: Causes, Signs, Symptoms, Diagnosis
• Treatment & Stages of Peritoneal Mesothelioma