Mesothelioma is a type of lung cancer that is virtually exclusively caused by exposure to asbestos or erionite - it is typically found in the mesothelium, the outer lining of the lungs. Most people who get mesothelioma, do so by inhaling asbestos fibers or being exposed to its dust at work. When there is no history of asbestos exposure at work, it is usually because another member of the household worked in an area with asbestos. Erionite is a natural mineral fiber found in volcanic ash and rock formations, it is similar to asbestos. According to the NIH (National Institutes of Health), it has been identified in 12 US states.
In this study, the authors describe two American families with a high incidence of mesothelioma and other cancers - linked to the BAP1 gene mutation.
Mesothelioma, one of the most aggressive and deadliest cancers, is responsible for approximately 3,000 deaths in the USA annually. Over 50% of patients die within a year of diagnosis. In Europe and China mesothelioma incidence has been rising for the last ten years.
Michele Carbone, M.D., Ph.D., study leader and director of the University of Hawaii Cancer Center, said:
"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. 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."
Study co-leader, Joseph R. Testa, Ph.D., and chair in Human Genetics at Fox Chase Cancer Center, Kenneth E. Weg, said:
"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 authors believe that the gene mutations are probably associated with several cancers - they found evidence of a link to breast, renal, and ovarian cancer risk.
Only about 1 in every 10 women with an inherited risk of ovarian or breast cancer have the BRCA1 or BRCA1 gene mutations - these genes raise the risk of developing the diseases. Therefore, BAP1 genes may also be involved in the inherited risk of ovarian and breast cancers.
"Also, it appears likely that other genes, in addition to BAP1, will be found to be associated with elevated risk of mesothelioma."
When the scientists started to detect genetic alterations in or near other stretches of DNA where the BAP1 gene is located, they wondered whether it may form part of a family history trait (for mesothelioma).
They examined two families with high incidences of mesothelioma more closely and found that samples from family members with mesothelioma or melanoma of the eye carried BAP1 gene mutations. They then sequenced the gene in 26 people who did not have a history of mesothelioma but had the disease - 25% of biopsies from tumors had the genetic mutations. In both mesothelioma patients who had inherited mutations, they had already had melanoma of the eye.
Donald Blair, Ph.D., NCI, said:
"The discovery that the BAP1 gene is involved in a new cancer syndrome characterized especially by uveal melanoma and mesothelioma provides yet another example of the critical importance of the detailed genetic analysis of human tumors. Such analysis can lead to the discovery of genes involved in the same tumors that arise spontaneously. This is an important advance in developing our understanding of the biological mechanisms underlying these tumors."