NIH-FUNDED RESEARCHERS DISCOVER GENETIC LINK TO MESOTHELIOMA
Identified gene mutation may underlie other cancer types

UH Cancer Center scientists have found that individuals who carry a mutation in a gene called BAP1 are susceptible to developing two forms of cancer – mesothelioma, and melanoma of the eye.  Additionally, when these individuals are exposed to asbestos or similar mineral fibers, their risk of developing mesothelioma, an aggressive cancer of the lining of the chest and abdomen, may be markedly increased.

The study, published online Aug. 28, 2011, in Nature Genetics, describes two U.S. families with a high incidence of mesothelioma, as well as other cancers, associated with mutations of the BAP1 gene.  The research was funded by the National Cancer Institute (NCI), part of the National Institutes of Health, and led by scientists at the University of Hawaii Cancer Center in Honolulu, and Fox Chase Cancer Center in Philadelphia.

Mesothelioma tumors are typically associated with asbestos and erionite exposure. Erionite, a naturally occurring mineral fiber similar to asbestos, is found in rock formations and volcanic ash. Deposits have been located in at least 12 states.

Only a small fraction of individuals exposed to erionite or asbestos actually develop mesothelioma, one of the deadliest forms of cancer that kills about 3,000 people each year in the United States, with half of those diagnosed dying within one year. Additionally, rates of new cases of mesothelioma in parts of the world, including Europe and China, have risen steadily over the past decade.

“This discovery is a first step in understanding the role of the BAP1 gene and its potential utility when screening for mutations in those at high risk,” said Michele Carbone, M.D., Ph.D., study leader and director of the University of Hawaii Cancer Center.  “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.”

Joseph R. Testa, Ph.D., study co-leader and Carol and Kenneth E. Weg chair in Human Genetics at Fox Chase Cancer Center, added, “This is the first study to demonstrate that individual genetic makeup can greatly influence susceptibility to mesothelioma. People exposed to dangerous levels of asbestos or erionite, those with a strong family history of mesothelioma, or those who have been previously diagnosed with a rare tumor of the eye known as uveal melanoma, may benefit from this new discovery.”

The study found evidence that some people with BAP1 gene mutations also developed breast, ovarian, pancreatic or renal cancers, suggesting the gene mutation may be involved in multiple cancer types.  Only about 10 percent of women with an inherited risk of breast or ovarian cancer carry mutations in the genes BRCA1 or BRCA2, which are known to be associated with those diseases. Consequently, some inherited risk of breast and ovarian cancer may stem from mutations in BAP1 genes.