Category: Research
Genetic Predisposition to Mesothelioma Observed by Cancer Researchers
By Wade Rawlins
People who carry a mutation in a certain gene are susceptible to developing mesothelioma and exposure to asbestos may significantly increase the risk of developing the life-threatening respiratory cancer, according to new research funded by the National Cancer Institute.
The study published in Nature Genetics reports on two American families with a high incidence of mesothelioma as well as other cancers associated with mutations of the BAP1 gene. It is the first study to demonstrate that family genetic makeup can influence susceptibility to mesothelioma, a cancer of the lining of the lung and abdomen. The discovery may lead to early detection and benefit people who have been exposed to asbestos in the workplace, people with a family history of mesothelioma and individuals who have previously been diagnosed with a rare tumor of the eye known as uveal melanoma.
Mesothelioma takes the lives of about 3,000 people a year in the U.S. The incidence of mesothelioma has risen steadily in the last decade in some parts of the world, including Europe and China. Yet, only a small portion of people exposed to asbestos or eronite, another mineral fiber similar to asbestos, develop symptoms of mesothelioma.
Scientists at the University of Hawaii Cancer Center in Honolulu and Fox Chase Cancer Center in Philadelphia followed two extended families with unusually high rates of mesothelioma for 14 years. The researchers suspected that mutations of the BAP1 gene, which is involved in tumor suppression, might underlie mesothelioma in people with a strong family history of the disease after noticing genetic changes in or near stretches of DNA where the BAP1 gene is located.
When the scientists looked more closely, they saw that every person who had provided a DNA sample and had developed mesothelioma or melanoma of the eye also carried mutations in the BAP1 gene.
The researchers then studied the genetic makeup of 26 patients diagnosed with mesothelioma who did not have a known family history of asbestos-related disease. They observed that tumors in about a fourth of the patients contained mutations in the BAP1 gene. In two cases, the mutations were inherited. Both of the individuals with inherited mutations had previously developed melanoma of the eye.
“The discovery is the 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., director of the University of Hawaii Cancer Center in a prepared statement. “Identifying people at greatest risk for developing mesothelioma, especially those exposed to dangerous levels of asbestos and eronite worldwide, is a task made easier by virtue of this discovery.”
People in jobs in which asbestos is an occupational hazard such as mining, shipbuilding, maintenance, plumbing and electrical work have a higher incidence of asbestos-related disease.
The study found evidence that some individuals with the BAP1 gene mutations also developed breast, ovarian, pancreatic and renal cancers, suggesting the gene mutation may be involved in multiple cancer types, also known as a cancer syndrome. About 10 percent of women with an inherited risk of breast or ovarian cancer carry mutations in the genes BRCA1 or BRCA2, which are associated with those diseases. Some inherited risk of breast or ovarian cancer may be associated with mutations in the BAP1 gene.
Just as breast cancer is linked to more than one gene mutation, Fox Chase scientists Joseph R. Testa, who led the study with Carbone, said that it appears likely that other genes in addition to BAP1 will be found to be linked with elevated risk of mesothelioma.
Hawaii Researchers’ Efforts to Crack Mesothelioma Code Aided by $3.5m Gift
Michele Carbone, director of the University of Hawaii Cancer Center and his colleagues, have made a series of recent scientific breakthroughs in understanding the mechanism by which asbestos triggers mesothelioma, an aggressive cancer of the lining of the lung and abdomen.
In recognition of that groundbreaking research, an anonymous donor has given the University of Hawaii Cancer Center a $3.58 million gift to support mesothelioma research, the university announced this month. The gift is the second largest in UH Cancer Center history.
“Mesothelioma is a serious public health problem,” said Virginia Hinshaw, chancellor of the University of Hawaii Manoa. “We’re proud that Dr. Carbone’s team is leading the world in this area of discovery. This gift validates their efforts and will help them remain at the forefront of thoracic oncology research.”
Closely associated with inhaling airborne asbestos fibers, mesothelioma produces an aggressive type of tumor. The current median survival from diagnosis is just 12 months, creating a need for more effective therapies to extend mesothelioma patients’ lives. Approximately 2,500 to 3,000 people in the U.S. are diagnosed with mesothelioma each year. Most were exposed to asbestos decades before cancer symptoms appeared.
Dr. Carbone and colleagues including Assistant Professor Haining Yang and Adjunct Professor Giovanni Gaudino have studied asbestos-related disease for more than a decade, analyzing how genetics, environmental carcinogens and viral infection interact to cause malignant mesothelioma.
In an article in the Proceedings of the National Academy of Sciences, Carbone and colleagues described how asbestos killed cells through a process called programmed cell necrosis that leads to the release of a protein molecule HMGB1. People exposed to asbestos have elevated levels of the protein in their blood. The protein begins an inflammatory chain reaction in tissue that causes the release of mutagens that promote tumor growth. Cancer often occurs in the presence of chronic inflammation. By interfering with the inflammatory reaction, it may be possible to decrease the occurrence of mesothelioma.
Many of the UH researchers’ findings have been based on work conducted in the villages of Capadoccia, a region of Turkey that has an extraordinarily high rate of mesothelioma deaths. Nearly 50 percent of the region’s residents develop and die of mesothelioma from exposure to eronite, a naturally occurring mineral fiber found in rock formations that is even more toxic than asbestos. Eronite has been used in the U.S. in road paving.
Drs. Carbone and Yang plan to conduct a clinical trial co-sponosored by the U.S. National Cancer Institute in Cappadocia to validate the serum biomarkers they discovered for the early detection of mesothelioma.
Their findings may have applications far beyond the villages of Turkey and lead to new ways to prevent and treat the disease. In the future, treatment approaches aimed at identifying people who are likely to develop mesothelioma based on elevated biomarkers and blocking chronic inflammation could reduce the risk of mesothelioma among workers exposed to asbestos.
“This generous gift is critical to support our efforts to generate discoveries that will aid in the prevention of mesothelioma and the development of new therapies,” Dr. Carbone said in a statement.
Asian Asbestos Tsunami Forecast
The number of people in Asia who develop mesothelioma and other asbestos-related diseases will increase sharply in the next two decades new research projects.
According to the study in Respirology, the journal of the Asian Pacific Society of Respirology, the increase in asbestos use in Asian countries since 1970 is likely to trigger a surge in asbestos-related disease in the next 20 years. Mesothelioma, a cancer of the lining of the lung, is a signature disease of asbestos. But workers exposed to asbestos typically take 20 to 50 years to experience symptoms of mesothelioma or lung cancer after inhaling microscopic asbestos fibers.
Dr. Ken Takahashi, the lead author and acting director of the World Health Organization Collaborative Center for Occupational Health, said that Asian governments should brace for an “asbestos tsunami” in the years ahead.
Asia’s share of worldwide asbestos use has steadily increased from 14 percent in the decades before 1970 to 64 percent from 2001 to 2007, the study said. Yet, the 12,882 deaths attributed to asbestos-related disease in Asia account for only 13 percent of the overall deaths linked to asbestos during the period.
In Asia, asbestos, a mineral fiber, is still widely used in building materials, roofing, cement and power plants. Many Asian countries that import asbestos have weak or non-existent workplace safety laws, leaving workers exposed to asbestos.
In the United States and Europe, most uses of asbestos have been banned since the late 1970s and workers must wear safety equipment to prevent inhaling asbestos.
The World Health Organization identifies asbestos as a dangerous workplace carcinogen and occupational hazard. It called for a worldwide ban on asbestos. An estimated 107,000 people die from asbestos-related diseases annually including approximately 3,000 in the U.S.
What the Veterans’ Cancer Registry Reveals About Mesothelioma
Doctors still have much to learn about mesothelioma and how best to treat patients diagnosed with this aggressive cancer linked with asbestos exposure.
To better understand the causes and consequences of mesothelioma, researchers from Creighton University School of Medicine and the Thomas Jefferson School of Medicine in Philadelphia retrospectively reviewed the medical records of 924 veterans diagnosed with malignant pleural mesothelioma between 1995 and 2009 and listed in the Veterans Affairs Cancer Registry.
The median age of the veterans with malignant pleural mesothelioma was 71, according to the researchers who presented their findings at the American Society of Clinical Oncology conference June 3-7 in Chicago. The median age of the veterans with mesothelioma is a reminder of the typical 20-year to 50-year delay between exposure to asbestos and appearance of asbestos disease symptoms. Many veterans of the Army, Navy, Air Force, Marines and Coast Guard likely were exposed to asbestos in their 20s and 30s, but didn’t notice any respiratory symptoms for decades.
From the 1940 through the 1970s, millions of veterans were exposed to asbestos which was widely used in building materials, automotive parts, ships and insulation. The use of asbestos was restricted starting in the late 1970s because of its toxicity to humans. According to the U.S. Department of Veterans Affairs, veterans who served in shipyards, mining, insulation work, carpentry and construction, demolition of old buildings, and the manufacture of friction products such as brakes were most likely exposed to asbestos.
In the new study published in the Journal of Clinical Oncology, the researchers reported that the median survival for the veterans with mesothelioma was seven months. Veterans who had malignant mesothelioma that had not spread and underwent surgery or surgery combined with chemotherapy or radiation tended to live longer.
Nearly 90 percent of veterans diagnosed with malignant pleural mesothelioma were Caucasian and about 9 percent were African American.
In the analysis, some factors observed among the veterans correlated with longer survival including younger age, diagnosis of early stage cancer, the type of cellular structure of the mesothelioma and receipt of surgery.
Approximately, 3,000 people are diagnosed with mesothelioma in the U.S. each year. Most are workers and veterans who were exposed to asbestos for an extended period on the job decades ago.
Renal Cancer Drug May Give Mesothelioma Patients New Treatment Option
Researchers in Austria report in the May issue of the Journal of Thoracic Oncology that a drug used to treat kidney cancer may also be a promising treatment for mesothelioma, a cancer linked to asbestos exposure.
Approximately 3,000 people are diagnosed with mesothelioma each year in the U.S. Many are workers who were exposed to asbestos dust in the workplace decades ago. Symptoms typically don’t appear for 20 to 40 years after exposure.
In a pre-clinical study, cancer researchers at the Medical University of Vienna say that a drug called temsirolimus may slow the growth of malignant pleural mesothelioma, a cancer that often resists chemotherapy and radiation.
Temsirolimus works by blocking the action of a protein that regulates cell growth, including cells in cancerous tumors. The drug is commonly used to treat patients with advanced kidney cell carcinoma.
The researchers said that temsirolimus, a kinase inhibitor, had a growth stopping effect on all mesothelioma cells by inhibiting the major oncogene known as mTOR. Oncogene are genes that cause the transformation of normal cells into cancerous tumor cells.
They said the mesothelioma cells that resisted the chemotherapy drug cisplatin, showed hypersensitivity to temsirolimus. That offers the potential that it may be a promising treatment strategy in combination with chemotherapy or as a second-line treatment.
Professor Walter Berger, of the Institute of Cancer Research at the Medical University of Vienna told the International Association for the Study of Lung Cancer that the results suggested that clinical trials should be undertaken on drugs that inhibit mTOR as a new mesothelioma treatment strategy.
Free Mesothelioma Patient & Treatment Guide
We’d like to offer you our in-depth guide, “A Patient’s Guide to Mesothelioma,” absolutely free of charge.
It contains a wealth of information and resources to help you better understand the condition, choose (and afford) appropriate treatment, and exercise your legal right to compensation.
Download Now