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Asbestos refers to a family of mineral fibers1 with varying carcinogenic potency. Thus far, crocidolite is the most potent type of Malignant Mesothelioma-causing asbestos. Erionite, a zeolite mineral fiber, is the most potent fiber in causing Malignant Mesothelioma.4 While occupational exposure to asbestos in the US and some other countries has been significantly reduced following the implementation of regulatory measures in the 80s, the anticipated decline in Malignant Mesothelioma incidence has not been observed.2

Dr. Carbone's research team has shown that environmental exposure caused by human development in areas containing geological deposits of asbestos and erionite is increasing and is associated with increased Malignant Mesothelioma incidence. Their studies in Cappadocia, Turkey and North Dakota (ND) identified exposure to asbestos and erionite, and they worked with local and national government authorities and the Environmental Protection Agency (EPA) to implement measures to minimize exposure that are expected to prevent Malignant Mesothelioma in future generations.4 Recently the team discovered extensive exposure to asbestos in the environment in Clark County (NV) that may be associated with increased incidence of Malignant Mesothelioma in young adults.6

Feature: 2011 Video Showing Dr. Carbone's Field Work in the US and Turkey


Future Research Plans

Identify Malignant Mesothelioma caused by environmental exposure and implement preventive strategies.

Dr. Carbone hypothesizes that the increased development of rural areas is leading to increased environmental exposure to mineral fibers and therefore to the development of Malignant Mesothelioma in exposed individuals. The identification of areas where people are exposed to asbestos and erionite from the environment allows the implementation of preventive strategies to decrease exposure and the risk of Malignant Mesothelioma.

Dr. Carbone's previous work has resulted in public health measures that minimized environmental exposure to carcinogenic mineral fibers and are expected to reduce the number of new Malignant Mesothelioma cases diagnosed in Cappadocia, Turkey,7 and in North Dakota.4 Dr. Carbone's team have recently identified an area of environmental risk in Nevada5 and plan to identify the locations where asbestos is present, characterize carcinogenicity of asbestos forms present in those locations, geomap the distance of the source of exposure to the residence of young adults who developed Malignant Mesothelioma to understand the impact of exposure, enroll subjects in biomarkers studies for early detection of Malignant Mesothelioma, and work with state authorities to design and implement measures to reduce exposure to asbestos. They also aim to extend this work to other states, where areas of carcinogenic mineral fiber deposits are known to exist.

REFERENCES

  1. Carbone M, Ly BH, Dodson RF, Pagano I, Morris PT, Dogan UA, Gazdar AF, Pass HI, Yang H. Malignant mesothelioma: Facts, myths and hypotheses. Malignant mesothelioma: Facts, myths and hypotheses. Journal of  Cellular Physiology, 227: 44-58, 2012 Jan. PMCID: PMC3143206.
  2. Henley SJ, Larson TC, Wu M, et al. Mesothelioma incidence in 50 states and the District of Columbia, United States, 2003-2008. International Journal of Occupational and Environmental Health 2013;19:1-10.
  3. Flores RM, Pass HI, Seshan VE, Dycoco J, Zakowski M, Carbone M, Bains MS, Rusch VW. Extrapleural Pneumonectomy Versus Pleurectomy Decortication in the Surgical Management of Malignant Pleural Mesothelioma. Journal of Thoracic Cardiovascular Surgery, 2008.
  4. 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. Erionite exposure in North Dakota and Turkish villages with mesothelioma. Proceedings of the National Academy of Science USA, 108:13618-23, 2011.
  5. Baumann F, Buck BJ, Metcalf RV, McLaurin BT, Merkler D, and Carbone M. The presence of asbestos in the natural environment is likely related to mesothelioma in young individuals and women from Southern Nevada. Journal of Thoracic Oncology, 10:731-7, 2015.
  6. Yang H, Rivera Z, Jube S, Nasu M, Bertino P, Goparaju C, Franzoso G, Lotze MT, Krausz T, Pass HI, Bianchi ME, and Carbone M. Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation. Proceedings of the National Academy of Science USA, 107: 12611-12616, 2010. PMCID: PMC2906549.
  7. Carbone M, Emri S, Dogan U, Steele I, Tuncer M, Pass HI, Baris YI. A mesothelioma epidemic in Cappadocia: scientific developments and unexpected social outcomes. Nature Reviews Cancer, 7:147-154, 2007.
  8. Roushdy-Hammady I, Siegel J, Emri S, Testa JR and Carbone M. A genetic-susceptibility factor malignant mesothelioma in the Cappadocian region of Turkey. The Lancet, 357:444-445, 2001.
  9. Dogan UA, Baris YI, Dogan M, Emri S, Steele I, Elmishad AG, and Carbone M. Genetic Predisposition to Fiber Carcinogenesis Causes a mesothelioma Epidemic in Turkey. Cancer Research, 66:5063-5068, 2006.
  10. Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox N, Dogan AU, Pass, HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, and Carbone M. Germline BAP1 mutations predispose to malignant mesothelioma. Nature Genetics, 43: 1022-25, 2011.
  11. Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. Bap1 and cancer. Nature Review Cancer, 13:153-159, 2013.
  12. Napolitano A, Pellegrini L, Dei A, Larson D, Tanji M, Flores EG, Kendrick B, Lapid D, Powers A, Kanodia S, Pastorino S, Pass HI, Dixit V, Yang H, and Carbone M. Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma. Oncogene, Advance online publication, June 29, 2015.
  13. Pena-Llopis S, Vega-Rubin-de-Celis S, Liao A, et al. BAP1 loss defines a new class of renal cell carcinoma. Nature Genetics, 2012;44:751-759.
  14. Carbone M, Ferris LK, Baumann F, Napolitano A, Lum CA, Flores EG, Gaudino G, Powers A, Bryant-Greenwood  P, Krausz T, Hyjek E, Tate R, Friedberg J, Weigel T, Pass HI, Yang H.  BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs.  Journal of Translational Medicine, 10:179, 2012.
  15. Baumann F, Flores E, Napolitano A, Kanodia A, Taioli E, Pass H, Yang H, and Carbone M. Mesothelioma Patients with Germline BAP1 Mutations Have Seven-Fold Improved Long-term Survival. Carcinogenesis, 36:76-81, 2015.
  16. Carbone M, Flores EG, Emi M, Johnson TA, Tsunoda T, Behner D, Hoffman H, Hesdorffer M, Nasu M, Napolitano A, Power A, Minaai M, Baumann F, Bryant-Greenwood P, Lauk O, Kirschner MB, Weder W, Opitz I, Pass HI, Gaudino G, Pastorino S, Yang H. Combined genetic and genealogic studies uncover a large BAP1 cancer syndrome kindred, tracing back nine generations to a common ancestor from the 1700s. PLoS Genetics, Advance online publication, Dec 18, 2015
  17. Napolitano A, Antoine DJ , Pellegrini L, Baumann F, Pagano IS , Pastorino S, Goparaju CM, Prokrym K, Canino C, Pass HI, Carbone M.  and Yang H. HMGB1 and its hyper-acetylated isoform are sensitive and specific serum biomarkers to detect asbestos exposure and to identify mesothelioma patients. Clinical Cancer Research, Advance online publication, Jan 5, 2016.
  18. Nasu M, Emi M, Pastorino S, Tanji M, Powers A, Baumann F, Zhang YA, Gazdar A, Kanodia S, Tiirikainen M, Flores E, Gaudino G, Becich GJ, Pass HI, Yang H, and Carbone M. High incidence of somatic BAP1 alterations in sporadic malignant mesothelioma. Journal of Thoracic Oncology, 10:565-76, 2015.
  19. Carbone M., et al. Consensus Report of the 2015 Weinman International Conference on Mesothelioma. Journal of Thoracic Oncology, accepted
  20. Carbone M and Yang H. Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma. Clinical Cancer Research, 18:598-604, 2012.
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