Researchers Find New Mesothelioma Genes in Family Study
August 6, 2018
The leading cause of malignant mesothelioma (MM) is exposure to asbestos. Despite this, only a small portion of people in routine contact with the mineral develop the cancer.
Research published June 30 in the journal Familial Cancer adds to the understanding of why some asbestos-exposed people develop mesothelioma, but most do not.
By carefully examining the genetic makeup of one family with several cases of malignant mesothelioma, the study authors identified new genes that may increase the risk of developing this rare cancer.
“This study strengthens the suspicion that, next to germline BAP1 alterations, other genetic factors might predispose families to the development of MM,” the authors wrote.
Mutations in only one gene called BAP1 have been shown to increase risk of mesothelioma. However, experts suspect other genes may play a role in the disease.
This new study supports the idea that other genes can predispose a person — or even an entire family — to mesothelioma.
Hints of Genetic Influence on Mesothelioma Risk
Asbestos exposure is the No. 1 cause of mesothelioma.
However, some families seem to have more cases of mesothelioma than can be explained by shared asbestos exposure alone.
After occupational exposure to asbestos, the lifetime risk of mesothelioma is up to 10 percent in these family members.
Yet among the general population, only around 2 to 4 percent of people with this type of exposure develop the disease.
The higher-than-expected mesothelioma risk seen in these families suggest genetic factors are making them more susceptible to the damaging effects of asbestos.
Most Family Members Exposed to Asbestos
Doctors first identified a Belgian family with a strong history of mesothelioma in 2014.
A 60-year-old male family member was diagnosed with malignant pleural mesothelioma (MPM) at this time.
The health care team collected personal and family medical histories from the patient. This revealed other family members who had been diagnosed with MM.
Given the rarity of mesothelioma — even among people with heavy asbestos exposure — multiple cases in one family pointed to the possibility of genetic factors for the disease.
Nearly all family members had some exposure to asbestos. Family members worked in a company that recycled asbestos-storage bags made of jute, a rough fiber made from the stems of a tropical plant.
Some family members did this work consistently for 20 to 25 years, while others helped during holidays only. A mother and grandmother were exposed occasionally when repairing torn bags.
Family Affected by Mesothelioma and Other Cancers
The 60-year-old patient’s brother died of MPM at age 47. His uncle died of peritoneal mesothelioma at age 52.
The patient shared his father had died from Hodgkin’s lymphoma at age 52, and his cousin died from esophageal cancer at age 53.
It is not uncommon for “cancer genes” to predispose a person or family to more than one type of cancer. Having cases of other cancer types in addition to mesothelioma in the family would not be unexpected.
Ruling Out Known Genetic Risk of BAP1 Gene
The doctors did a complete genetic analysis on the patient and his tumor. None of the other cancer-affected relatives were alive, so the researchers could not complete a genetic analysis for these individuals.
Four living family members that have not been diagnosed with cancer provided blood for genetic analysis.
The study authors found no mutations in BAP1, the known gene mutation associated with increased mesothelioma risk.
After ruling out BAP1 as a cause of mesothelioma in this family, researchers identified 11 other possible gene mutations that could lead to increased cancer risk.
Honing in on Possible Genetic Contributors to Mesothelioma
Of these identified genes, one in particular stood out: RBM15.
This gene is associated with other cancers, including certain types of leukemia and ovarian cancer. It is not commonly mutated in the general population.
The study did not prove RBM15 mutations caused mesothelioma and other cancer in this family. However, researchers believe other genetic factors may be at play.
“The high prevalence of MM and other primary malignancies [Hodgkin’s lymphoma and esophageal cancer] in this family remains striking and points towards the possible involvement of other predisposing genetic factors,” the authors wrote.
Research Bolsters Idea of Other Genetic Risk Factors
Mesothelioma experts know of mutations in only one gene — BAP1 — that are strongly associated with increased risk of mesothelioma.
But the disease clusters in families that do not have BAP1 mutations, suggesting other genes play a role in mesothelioma risk.
Having a better understanding of which additional genes are problematic would allow affected families and family members to undergo genetic testing.
This may allow for better screening and the chance to catch mesothelioma early, when the cancer is most treatable.
Genetic testing for BAP1 already is being studied in clinical trials, demonstrating the potential benefits for people affected by mesothelioma.