Northeast Pennsylvania Polycythemia Vera (PV) Investigation

Background

In 2004, using state cancer registry records, the Pennsylvania Department of Health (PADOH) found a PV cluster in northeast Pennsylvania. PV is part of a disease group called myeloproliferative neoplasms (MPN), which is a group of slow-growing blood cancers where the bone marrow makes too many red blood cells, white blood cells, or platelets.

In 2006, ATSDR was asked to help study PV patterns in the area. From 2007-2008, ATSDR reviewed medical records, conducted genetic testing, and confirmed this PV cluster.

In 2009, Congress funded ATSDR to continue this investigation. ATSDR is overseeing 18 projects with PADOH, the Pennsylvania Department of Environmental Protection, and various universities and private organizations. These projects are based on recommendations from an expert panel. The panel identified four areas for investigation; epidemiology, genetics, toxicology, and environmental studies.

In 2014, the last of the contracts for the 18 different projects ended.

PV Research Projects Status Graphic March 2015  (The Graphic)

Status

The graphic, PV Research Projects Status Graphic March 2015  (The Graphic),  this provides a summary of the status of each of the 18 projects as of March 2015.  I’ve attached this graphic both as a “snapshot” in the body of this email, as well as a pdf attachment.  Projects highlighted in “green” in the attached graphic have work complete and a final product available (if applicable).  Projects highlighted in “yellow” have final products in progress and undergoing clearance.  Projects highlighted in “red” have final products that are anticipated but not yet started.  The shapes of the projects in the graphics give you an idea of the category of work of that project, as described in the key on the graphic.

As of March 23, 2015, work is complete and a final product is available (if applicable) for 12 projects.  We are happy to announce that 1 new project (#12) moved from yellow to green since my January 2015 update:

#12:  “Tri-County MPN Updated Surveillance Study“ conducted by the University of Pittsburgh is complete.  The published manuscript and ATSDR/CDC summary factsheet are available on the ATSDR website at:

http://www.atsdr.cdc.gov/sites/polycythemia_vera/

The purpose of this study was to examine PV reporting to the Pennsylvania Cancer Registry (PCR) following the original ATSDR PV investigation; to determine whether other myeloproliferative neoplasms (MPNs) were similarly underreported or falsely reported; and to determine whether a cancer cluster persisted in the follow-up period. The original ATSDR PV cancer cluster investigation was conducted in a tri county area in northeast Pennsylvania in 2006. This study was initiated to update and expand the original investigation.  These researchers found that:

• *       Most MPN cases had been reported to the PCR but only about half were true cases.
• *       Using the seven true PV cases identified, these researchers did not find any statistically significant clusters in space or in space-time in this updated analysis.
• *       Using the eleven true CML cases, these researchers did not find any statistically significant clusters in space or in space-time in this updated analysis.
• *       Using nine true ET cases, these researchers found a statistically significant cluster at the zip-code level when evaluated in space, but not in space-time.
• *       The estimated incidence rates for most MPNs are lower than the rates calculated from the original PCR database.
• *       The estimated PV incidence rate was 2.5 (0.8-5.1) per 100,000, 64% lower than the original rate based on PCR reports after correcting for completeness and accuracy.
• *       The estimated ET incidence rate was 2.3 (0.6-3.8) per 100,000, slightly higher than the original rate based on PCR reports after correcting for completeness and accuracy.
• *       However, the wide range of values for estimated incidence rates reflects the variability associated with the findings based on the low response rate. The response rate for this study was 26%. This means that approximately ¼ of the identified cases agreed to participate in this study.

Further, #13 “Case Control Study” conducted by Drexel University (reported as already complete when Carol Ann Gross-Davis’ PhD dissertation was completed as of the October 2014 update) now has a publicly available journal article published related to this effort.  This article is entitled “The Role of Genotypes That Modify the Toxicity of Chemical Mutagens in the Risk for Myeloproliferative Neoplasms” and is available online at:

http://www.mdpi.com/1660-4601/12/3/2465/html

This article describes Drexel’s population-based case-control study.  Eligible participants were residents of Carbon, Luzerne, and Schuylkill counties born between 1921–1968 and residing in the area between 2000–2008. Drexel recruited 27  “cases” (i.e., participants diagnosed with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF))and 292 “controls” (i.e., participants not diagnosed with MPNs but similar in other characteristics such as age, residence history, etc) through random digit dialing.  Blood samples from participants were analyzed, and odds ratios estimated for a select set of polymorphisms (i.e., variations in a particular DNA sequence).  The researchers selected polymorphisms that are associated with “environmentally sensitive genes.”  The aim of this effort was to try to identify potential classes of environmental exposures that could be linked to the development of genetic changes that could be related to MPNs.

For more information:

Visit ATSDR’s web page on PV: http://www.atsdr.cdc.gov/sites/polycythemia_vera/index.html

Call ATSDR’s toll-free PV information line: 866-448-0242 or email jcx0@cdc.gov, which will connect you to Dr. Elizabeth Irvin-Barnwell, ATSDR Division of Toxicology and Human Health Sciences.

Contact Lora Siegmann Werner, ATSDR Region 3, by phone at 215-814-3141 or by email at lkw9@cdc.gov.