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Cancer researchers discover genetic link to mesothelioma

People exposed to asbestos who carry a mutation in a gene called BAP1 have a greater risk of developing pleural mesothelioma.


Researchers from the University of Hawaii Cancer Center and the Fox Chase Cancer Center in Philadelphia studied two families with unusually high rates of mesothelioma, a deadly cancer caused by exposure to asbestos. They found that every person who had the disease also carried mutations in the BAP1 gene, which previous research has identified as a tumor suppressor.


The researchers sequenced the gene in 26 people who had developed mesothelioma but did not have a family history of the disease. They found that five members in one family, each with a mutated form of BAP1, had malignant mesothelioma, breast, ovarian or renal cancer. Six members of the second family who had mesothelioma also displayed a BAP1 mutation that was not evident in healthy family members.


The study, published online August 28 in Nature Genetics, suggests BAP1 gene mutation may be involved in other cancer types. The researchers found an association between the mutation and increased risk of melanoma of the eye, along with evidence that some people with the mutation also developed breast, ovarian, pancreatic or renal cancers.


Mesothelioma kills 2,000-3,000 Americans each year. Heath officials estimate that 27 million U.S. workers were exposed to asbestos between 1949 and 1979, and they predict that because the disease can take decades to emerge after asbestos exposure, the rate of new cases will continue to rise.


The researchers began seeking genetic predispositions to mesothelioma because only a small fraction of people exposed to asbestos develop the disease, but prior evidence suggested that mesothelioma “clustered’ in some families. The findings are the first to show that individual genetic makeup is a significant factor in mesothelioma cases, said Joseph R. Testa, co-leader of the study, who studies human genetics at Fox Chase Cancer Center.


Study co-leader Michele Carbone, director of the University of Hawaii Cancer Center, said the research will help to identity people at high risk of mesothelioma who could be targeted for early intervention.


“Identifying people at greatest risk for developing mesothelioma, especially those exposed to dangerous levels of asbestos and erionite worldwide, is a task made easier by virtue of this discovery,” Carbone said.


The research was funded by the National Cancer Institute (NCI), part of the National Institutes of Health.