A Multidisciplinary Investigation of a Polycythemia Vera Cancer Cluster of Unknown Origin
Abstract
:1. Introduction
2. Results and Discussion
2.1. Epidemiologic Studies
2.1.1. Case control study (Drexel University School of Public Health)
2.1.2. Comparative epidemiologic study (University of Pittsburgh Cancer Institute)
2.1.3. PV and MPN surveillance (PADOH)
- PV Surveillance—PADOH will assess and classify cases of PV reported to the cancer registry from the tri-county area since the joint PADOH/ATSDR survey was conducted in 2005. Other counties in Pennsylvania reporting high rates of PV compared to the state average will also be evaluated. The PV diagnosis will be confirmed using 2008 WHO guidelines by reviewing medical records and offering a JAK2 analysis, if needed. Non-reported cases in the tri-county area will be identified through regional hematologists/oncologists.
- MPN Surveillance—The MPNs represent an inter-related series of diseases that may have a common origin, and CML, ET, and IM have not yet been evaluated in the tri-county area. Since there is an apparent excess of PV in the area, the other MPNs may be similarly elevated. Persons identified in the Pennsylvania Cancer Registry since 2001 with any of these three diseases will be assessed through questionnaires and will be offered genetic testing, if necessary, for validation of their diagnosis. Data in the registry related to these disorders from other areas of the Commonwealth will also be reviewed.
- Logistical/Technical Support—PADOH will assist other research partners by providing community outreach and support, local clinical laboratory services (where available), and logistical and technical assistance. This will include coordinating with community leaders; providing educational and informational materials to local residents; and offering clinical services to PV research partners, including blood draws, specimen storage and transfer to outside laboratories. PADOH will also assist research partners with data needs with respect to the cancer registry and other state databases.
2.1.4. Patterns of MPN diagnosis, reporting, and care (Geisinger Clinic)
2.1.5. Prospective study of JAK2-positive persons without MPN or with mild MPN in the tri-county area (Geisinger Clinic)
2.1.6. Enhancement of physician reporting of hematologic cancers, including PV, in the CDC supported National Program of Cancer Registries (Centers for Disease Control and Prevention)
2.1.7. Geospatial analysis of MPN residences (ATSDR)
2.2. Genetic and Biomarker Studies
2.2.1. JAK2 screening in the cluster area (ATSDR)
2.2.2. JAK2 prevalence study (Geisinger Clinic)
2.2.3. Gene profiling study (Mt. Sinai School of Medicine)
2.2.4. Tissue bank for cluster-area MPN patients (MPD-Research Consortium, New York)
2.3. Toxicology Studies
2.3.1. Bone marrow toxicological assay (Mt. Sinai School of Medicine)
2.4. Environmental Studies
2.4.1. Environmental exposure assessment data inventory (ATSDR)
- Environmental data, including types and locations of industries and hazardous waste sites; land use and cover; water use and distribution; air emission inventories and sources of air pollution; waste management information; and environmental sampling information for chemicals and radionuclides released into air, water, soil, and biota.
- Topographic data, including roads, water features, and base maps that define legal boundaries and serve as reference points.
- Demographic data, including the age, race, sex, education, and income of the population in the tri-county area.
- Health outcome data, including PV and MPN incidence and surveillance data, JAK2 screening and prevalence data, and other health conditions identified during the PV investigations.
2.4.2. Environmental testing (Pennsylvania Department of Environmental Protection)
- McAdoo Outflow Testing. Water and sediment samples will be collected from a minimum of 20 different locations at the McAdoo Associates site to provide data that describes the surface water and groundwater outflow to the south. The locations will be sampled for volatile organic compounds (VOCs), semi-volatile organic compounds (SVOCs), heavy metals, polychlorinated biphenyls (PCBs) and radioactivity at least two times over the period of 1 year to reflect seasonal variations.
- PV Residence Testing. Drinking water quality, soil, indoor dust, and residential radon levels will be tested at the current and past residences of confirmed PV patients and at a number of other sites in the cluster area. Samples will be tested for VOCs, SVOCs, heavy metals, PCBs, herbicides, pesticides and radioactivity.
- CoGeneration Water Monitoring Testing. Water samples will be collected from various locations at three waste coal CoGeneration plants in the study area. The selected sites will be sampled for VOCs, SVOCs, heavy metals, PCBs, radioactivity (gross alpha & beta), and other water chemistry parameters (e.g., nitrate/nitrite, fluoride, sulfates, alkalinity) on two separate occasions to reflect seasonal variations.
2.5. Community Involvement/Education Activities
2.5.1. Community Action Committee (Henry S. Cole & Associates)
2.5.2. Physician education (Geisinger Clinic)
2.6. Oversight and Management (ATSDR)
3. Conclusions
Acknowledgments
References
- Pennsylvania Department of Health, Tamaqua Area Cancer Incidence Study. 1996 through 2002. Bureau of Epidemiology, Pennsylvania Department of Health: Harrisburg, PA, USA, 2005.
- Rollison, DE; Howlader, N; Smith, MT; Strom, SS; Merritt, WD; Ries, LA; Edwards, BK; List, AF. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001–2004, using data from the NAACCR and SEER programs. Blood 2008, 112, 45–52. [Google Scholar]
- Tefferi, A. Polycythemia vera: A comprehensive review and clinical recommendations. Mayo. Clin. Proc 2003, 78, 174–194. [Google Scholar]
- Kralovics, R; Passamonti, F; Buser, AS; Teo, S; Tiedt, R; Passweg, JR; Tichelli, A; Cazzola, M; Skoda, RC. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N. Engl. J. Med 2005, 352, 1779–1790. [Google Scholar]
- Kralovics, R; Stockton, D; Prchal, J. Clonal hematopoiesis in familial polycythemia vera suggests the involvement of multiple mutational events in the early pathogenesis of the disease. Blood 2003, 102, 3793–3796. [Google Scholar]
- Landgren, O; Goldin, LR; Kristinsson, SY; Helgadottir, EA; Samuelsson, J; Bjorkholm, M. Increased risks of polycythemia vera, essential thrombocythemia, and myelofibrosis among 24,577 first-degree relatives of 11 039 patients with myeloproliferative neoplasms in Sweden. Blood 2008, 112, 2199–2204. [Google Scholar]
- Jones, AV; Chase, A; Silver, RT; Oscier, D; Zoi, K; Wang, YL; Cario, H; Pahl, HL; Collins, A; Reiter, A; Grand, F; Cross, NCP. JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms. Nat. Genet 2009, 41, 446–449. [Google Scholar]
- Olcaydu, D; Harutyunyan, A; Jager, R; Berg, T; Gisslinger, B; Pabinger, I; Gisslinger, H; Kralovics, R. A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms. Nat. Genet 2009, 41, 450–454. [Google Scholar]
- Kilpivaara, O; Mukherjee, S; Schram, AM; Wadleigh, M; Mullally, A; Ebert, BL; Bass, A; Marubayashi, S; Heguy, A; Garcia-Manero, G; Kantarjian, H; Offit, K; Stone, RM; Gilliland, DG; Klein, RJ; Levine, RL. A germline JAK2 SNP is associated with predisposition to the development of JAK2V617F-positive myeloproliferative neoplasms. Nat. Genet 2009, 41, 455–459. [Google Scholar]
- Smith, CA; Fan, G. The saga of JAK2 mutations and translocations in hematologic disorders: pathogenesis, diagnostic and therapeutic prospects, and revised World Health Organization diagnostic criteria for myeloproliferative neoplasms. Hum. Pathol 2008, 39, 795–810. [Google Scholar]
- Seaman, V; Jumaan, A; Yanni, E; Lewis, B; Neyer, J; Roda, P; Xu, M; Hoffman, R. Use of molecular testing to identify a cluster of patients with polycythemia vera in eastern Pennsylvania. Cancer Epidem. Biomarker. Prev 2009, 18, 534–540. [Google Scholar]
- Shuga, J; Zhang, J; Samson, LD; Lodish, HF; Griffith, LG. In vitro erythropoiesis from bone marrow-derived progenitors provides a physiological assay for toxic and mutagenic compounds. Proc. Nat. Acad. Sci. USA 2007, 104, 8737–8742. [Google Scholar]
- Aldrich, T; Sinks, T. Things to know and do about cancer clusters. Cancer Invest 2002, 20, 810–816. [Google Scholar]
Project | Period | Partner |
---|---|---|
Epidemiologic Studies | ||
Case-control study in the cluster area | 2 years | Drexel University School of Public Health |
Comparative epidemiologic study in western Pennsylvania | 2 years | University of Pittsburgh Cancer Institute |
PV and MPN surveillance in Pennsylvania | 3 years | Pennsylvania Department of Health (PADOH) |
Patterns of MPN diagnosis, reporting, and care | 3 years | Geisinger Clinic |
Prospective study of JAK2-positive non-MPN in the tri-county area | 3 years | Geisinger Clinic |
Enhancement of physician reporting of hematologic cancers in the CDC National Program of Cancer Registries | 3 years | Centers for Disease Control and Prevention (CDC) |
Geospatial analysis of MPN residences | 3 years | ATSDR |
Genetic and Biomarker Studies | ||
Gene profiling study | 3 years | Mt. Sinai School of Medicine |
JAK2 screening in the cluster area | 1 year | ATSDR |
JAK2 prevalence study | 1 year | Geisinger Clinic |
Tissue bank for cluster-area MPN patients | 3 years | MPD-Research Consortium |
Toxicology Studies | ||
Bone marrow toxicological assay | 3 years | Mt. Sinai School of Medicine |
Environmental Studies | ||
Environmental exposure assessment and data inventory | 2 years | ATSDR |
McAdoo superfund site outflow testing | 2 years | Pennsylvania Department of Environmental Protection (PADEP) |
Residential testing | 2 years | |
Cogeneration water monitoring testing | 2 years | |
Community Involvement/Education Activities | ||
Community action committee (CAC) | 2 years | Henry S. Cole & Associates |
Physician education | 3 years | Geisinger Clinic |
© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
Share and Cite
Seaman, V.; Dearwent, S.M.; Gable, D.; Lewis, B.; Metcalf, S.; Orloff, K.; Tierney, B.; Zhu, J.; Logue, J.; Marchetto, D.; et al. A Multidisciplinary Investigation of a Polycythemia Vera Cancer Cluster of Unknown Origin. Int. J. Environ. Res. Public Health 2010, 7, 1139-1152. https://doi.org/10.3390/ijerph7031139
Seaman V, Dearwent SM, Gable D, Lewis B, Metcalf S, Orloff K, Tierney B, Zhu J, Logue J, Marchetto D, et al. A Multidisciplinary Investigation of a Polycythemia Vera Cancer Cluster of Unknown Origin. International Journal of Environmental Research and Public Health. 2010; 7(3):1139-1152. https://doi.org/10.3390/ijerph7031139
Chicago/Turabian StyleSeaman, Vincent, Steve M. Dearwent, Debra Gable, Brian Lewis, Susan Metcalf, Ken Orloff, Bruce Tierney, Jane Zhu, James Logue, David Marchetto, and et al. 2010. "A Multidisciplinary Investigation of a Polycythemia Vera Cancer Cluster of Unknown Origin" International Journal of Environmental Research and Public Health 7, no. 3: 1139-1152. https://doi.org/10.3390/ijerph7031139