Environmental Factor, October 2011, National Institute of Environmental Health Sciences
Upcoming NIEHS workshop on erionite and mesothelioma
By Melissa Kerr
Miller and Carbone closed their PNAS paper by stressing, “[Prevention strategies] would be of immediate benefit to the population of North Dakota and other erionite-rich areas of the United States, to reduce the potential for disease and limit adverse effects among those already exposed.” (Photo courtesy of Steve McCaw)
NIEHS will host a workshop exploring the state-of-the-science surrounding the mineral erionite and its potential threat to human health Oct. 12 in Rodbell Auditorium. The interdisciplinary, interagency workshop was developed by NIEHS Senior Medical Advisor, Aubrey Miller, M.D.(http://www.niehs.nih.gov/about/od/advisor/miller/index.cfm), to educate scientists on the state of the science concerning erionite exposure and its public health implications (see text box).
Two recent NIH-funded studies underscore the importance to environmental health sciences of understanding more about this mineral, which has been found in at least 12 U.S. states.
Erionite and mesothelioma in North Dakota and Turkey
Exposure to erionite and the resulting malignant mesothelioma (MM) have been known to result in devastating effects on human health as seen in Turkish villages. In some of these Turkish villages 20-50 percent of all deaths are caused by MM. A new study(http://www.ncbi.nlm.nih.gov/pubmed/21788493) by an NIH-funded research team headed by Miller and Director of the University of Hawaii Cancer Center Michele Carbone, M.D., Ph.D.(http://www.crch.org/profiles/profilecarbone.htm) , found a link between what has been happening in Turkish villages and erionite exposures, and what could happen by mid-century in such places as Dunn County, N.D.
Dunn County is a place of interest because the North Killdeer Mountains there contain erionite. Within the county, approximately 300 miles of road have been paved using gravel from the erionite-containing mountains. As the researchers explain, “There are no health benchmarks established in the United States to regulate or provide guidance for use and exposures to erionite.”
Health concerns regarding this mineral may go unrecognized due to a latency period of 30 years or more between exposure and the development of MM, confounding by asbestos exposures, and the small number of exposed populations. Miller and his team took several air samples in various Turkish villages where increased MM was known to be associated with erionite as well as various places around Dunn County. The results show that many of the readings in North Dakota are comparable to those from the village of Boyali, Turkey where 6.25 per cent of all deaths are caused by MM.
The researchers called for the Early Detection Research Network of the National Cancer Institute (NCI) to begin working with the Turkish Ministry of Health in hopes of defining markers for early detection of MM. The authors said that resources need to be focused on studying exposure, genetics, mechanisms of toxicity, and prevention strategies. “Our findings,” the researchers concluded, “indicate that implementation of novel preventive and early detection programs in ND and other erionite-rich areas of the United States, similar to efforts currently being undertaken in Turkey, is warranted.”
Gene-environment interactions in malignant mesothelioma
In what Miller describes as a seminal paper(http://www.ncbi.nlm.nih.gov/pubmed/21874000) in the search for prevention strategies in regard to mesothelioma, Carbone led a team that explored the possibility of genetic predisposition in developing MM. The research team, funded in part by NCI, discovered that mutations in the BRCA1 associated protein-1 (BAP1) have a link with the development of MM and uveal melanoma, a cancer of the eye.
BAP1 is a nuclear protein that acts as a tumor suppressor in the BRCA1 growth control pathway. Carbone's team found that the mutations of BAP1 have a familial connection. He pointed out that mesothelioma clustering has been seen before in families from the U.S. and Turkey. The researchers sequenced BAP1 germline DNA and found that six individuals within the same family, who developed some kind of cancer, had identical mutations. Family members who were not affected did not show the same mutation.
The BAP1 mutation has been associated with not only mesothelioma and uveal melanoma, but it is believed to play a role in other cancers as well. The research suggests that persons who display this mutation are much more likely to develop mesothelioma when an exposure to asbestos occurs. The author suggests that even the BAP1 mutation itself could potentially be all that is necessary for a person to develop mesothelioma.
Understanding the role that BAP1 plays in the onset of mesothelioma, as well as the potential role in other cancers, may be a highly useful diagnostic tool. The authors conclude, “These findings will help to identify individuals at high risk of mesothelioma who could be targeted for early intervention.”
Citations: Carbone M, Baris YI, Bertino P, Brass B, Comertpay S, Dogan AU, Gaudino G, Jube S, Kanodia S, Partridge CR, Pass HI, Rivera ZS, Steele I, Tuncer M, Way S, Yang H, Miller A(http://www.ncbi.nlm.nih.gov/pubmed/21788493) . 2011. Erionite exposure in North Dakota and Turkish villages with mesothelioma. Proc Natl Acad Sci U S A. 108(33):13618-13623.
Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox NJ, Dogan AU, Pass HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, Carbone M(http://www.ncbi.nlm.nih.gov/pubmed/21874000) . 2011. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet; doi: 10.1038/ng.912 [Online 28 August 2011].
(Melissa Kerr studies chemistry at North Carolina Central University. She is currently an intern in the NIEHS Office of Communications and Public Liaison.)
Facing the potential health effects of erionite exposure
Erionite is a naturally occurring mineral that forms ultra-fine fibrous masses and can be found in rock formations. Erionite is a concern due to the fact that some of the properties of the material are similar to the properties of asbestos. There is concern that erionite may be associated with an increased risk of lung cancer and mesothelioma, a deadly cancer of the smooth lining of the chest, lungs, heart, and abdomen. According to the Centers for Disease Control and Prevention, between 1999 and 2005 there were 18,083 deaths in the United States attributed to malignant mesothelioma.
Miller hopes for a several outcomes from the workshop. Through a comprehensive discussion, he would like for interested stakeholders to have the ability to move forward with a standard base of knowledge concerning erionite. He also hopes to bring forth ideas for further research and collaboration. The final goal of the workshop is to specify short-term and long-term actions needed to “advance scientific understanding and help to address ongoing public health concerns.”
The workshop agenda is still being finalized. However, tentative topics and discussion leaders include:
- Mineralogy and Morphology, moderated by geologist Greg Meeker, of the U.S. Geological Survey (USGS) Denver Microbeam Laboratory(http://usgsprobe.cr.usgs.gov/newphotos.html)
- Exposure Assessment, moderated by NIEHS Toxicology Liaison Christopher Weis, Ph.D.(http://www.niehs.nih.gov/about/od/advisor/weis/index.cfm)
- Epidemiologic Research, moderated by James Lockey, M.D.(http://www.eh.uc.edu/dir_individual_details.asp?qcontactid=807) , of the University of Cincinnati
- Clinical and Genetics Research, moderated by Harvey Pass, M.D.(http://www.med.nyu.edu/cvsurgery/thoracic/faculty/bios/pass.html) , of the New York University Medical Center
- Mechanistic/Toxicology Research, moderated by Michele Carbone, M.D., Ph.D.(http://www.crch.org/profiles/profilecarbone.htm) , University of Hawaii Cancer Center.
- Public Health Concerns and Issues/Open Discussion, moderated by Stephen Levin, M.D.(http://www.asbestos.net/mesothelioma/doctors/dr-stephen-m-levin) , of the Mount Sinai School of Medicine
Representatives of several agencies interested in the problem of erionite and MM will be attending or participating by remote hook-up. They include staff from NIEHS, USGS, the U.S. Environmental Protection Agency, the National Institute for Occupational Safety and Health, the National Institute of Standards and Technology, and the National Toxicology Program. NIEHS/NTP Director Linda Birnbaum, Ph.D., is scheduled to give opening remarks.