The term “high-risk predisposition,” is a well-known term in the cancer world that means a person could have certain genetic factors or other factors that places him or her at a higher risk for certain cancers. For mesothelioma, a high risk factor is the mutated BAP1 gene: a tumor suppressor that is responsible for encoding DNA repair. However, many patients diagnosed with malignant mesothelioma do not have a BAP1 gene mutation, so scientists and researchers began to explore other genes that are involved in hereditary cancer syndromes that could lead to an inherited predisposition to mesothelioma.
Mesothelioma is a rare and aggressive cancer with an extremely poor prognosis that is caused by asbestos exposure. However, not everyone who has been exposed to asbestos will develop mesothelioma, even though their chances are significantly increased. For decades scientists and researchers have been trying to figure out what makes an individual more susceptible to developing mesothelioma over others, and thanks to a recent study published in Cancer Letters scientists are another step closer in honing in on the variants.
To do this, they looked at germline mutations, mutations passed from one generation to the next since that is the type of mutation on the BAP1 gene. These germline variants were investigated in 94 cancer-predisposing genes among 93 patients diagnosed with malignant pleural mesothelioma. These patients all had varied amounts of asbestos exposure. It was found that ten pathogenic variants were identified – all along the DNA repair pathways in close to 10% of the panel. Those in that 10% had the least amount of asbestos exposure.
Damage to the DNA repair pathways mean that cells damaged by asbestos fibers are unable to repair themselves and have a higher chance of developing a malignancy. This study further proves that there is no safe level of asbestos exposure because those who have a predisposition to the disease have a higher chance of being diagnosed regardless of how much he or she was exposed. The results of this study are also useful in determining the most effective treatment options because doctors will have a better understanding of the uniqueness of the disease to that particular individual.
Mesothelioma is difficult to treat as it is usually caught in the later stages of the disease, when the cancer is too advanced to be affected by any sort of medication or surgery. Early diagnosis is a key component in mesothelioma survival and scientists and researchers are continually exploring opportunities where they can diagnose mesothelioma in the beginning stages.
Source:
Betti, M, “Germline mutations in DNA repair genes predispose asbestos-exposed patients to malignant pleural mesothelioma,” Cancer Letters (July 4, 2017). [Link]
