Study Shows Link Between Agent Orange and MPNs
Employees of Traut Companies and a geologist with EA Engineering, Science, and Technology, Inc. prepare a core sample for analysis during a remedial investigation into the presence of Per- and Polyfluoroalkyl substances at Truax Field in Madison, WI, late last year. The investigation marks the second major step in the Environmental Protection Agency’s Comprehensive Environmental Response, Compensation, and Liability Act process which will guide the mitigation of PFAS compounds on and around the Air National Guard installation. U.S. Air National Guard photo by Isabella Jansen
A recent study has linked the development of polycythemia vera and other MPNs—essential thrombocythemia (ET) and primary myelofibrosis (MF)—with exposure to the herbicide Agent Orange. Among patients with MPNs, researchers reported, the likelihood of exposure to Agent Orange was 1.63 times higher compared to the exposure odds among controls.
WASHINGTON, DC—One of a group of rare blood disorders known as myeloproliferative neoplasms (MPNs), polycythemia vera (PV) is characterized by elevated absolute red blood cell mass due to uncontrolled red blood cell production. In most patients, the production of white blood cells and platelets are also elevated. If not controlled, this proliferation can lead to blood clots resulting in stroke and organ and tissue damage.
A mutation of the Janus kinase 2 gene (JAK2) is thought to be the most likely source of PCV pathogenesis. More than 90% of individuals with PCV have a mutation in the JAK2 gene. The exact role JAK2 mutations play in the development of PCV or what causes the mutations is not known, but a recent study links the development of PCV and other MPNs—essential thrombocythemia (ET) and primary myelofibrosis (MF)—with exposure to the herbicide Agent Orange.1
Named for the orange band around the barrel in which it was stored, Agent Orange was a tactical herbicide used by the U.S. military to control vegetation during the Vietnam War. The VA has recognized certain types of cancers and other diseases—including bladder cancer, Type 2 diabetes mellitus, hypertension and Hodgkin’s disease—as presumptive diseases associated with exposure to Agent Orange or other herbicides during military service. But the recent study is the first to show an association between Agent Orange and PCV and other MPNs.
To conduct the study, researchers led by Andrew Tiu, MD, a second-year hematology/oncology fellow with Medstar Georgetown University Hospital in Washington, DC, used the VA Informatics and Computing Infrastructure (VINCI) database to analyze the medical records of 93,269 MPN patients from a pool of 12,352,664 veterans spanning 17 years. To establish a comparative baseline, veterans from Illinois were included as a control group, chosen for its strong representativeness of the broader U.S. population, as per data from the U.S. Census Bureau.
Key findings included:
- Among patients with MPNs, the likelihood of exposure to Agent Orange was 1.63 times higher compared to the exposure odds among controls.
- When comparing individuals with MPNs to controls matched for age, gender, and race, there were higher incidences of arterial clotting (37% vs. 18.5%), venous clotting (14.8% vs. 5.2%), and bleeding events (39.1% vs. 13.5%) among the MPN patients, respectively.
- People with MPNs were more likely to have hypertension (75.5% vs 43.2%), diabetes (31.2% vs 19%) and heart failure (26.1% vs 11%) than age-, gender-, and race-matched controls, respectively.
- The odds of Agent Orange exposure among matched controls with arterial clots were 1.38 times greater than the odds of exposure among controls without arterial clots.
- The odds of Agent Orange exposure among patients with MPNs and arterial clots were 1.49 times greater than the odds of exposure among patients with MPNs without arterial clots.
As the team’s findings indicate potential associations rather than causation, Tiu emphasized the necessity for researchers to delve deeper into the biology of MPNs. Specifically, they want to look at JAK2 mutations. “There are several associations between Agent Orange and health disorders that are not well understood, and we hope our work helps uncover a few of these,” said Tiu said in a press release from Georgetown University’s Lombardi Comprehensive Cancer Center. 2
DoD Conducts Environmental Cleanup Efforts
The findings of this previously unknown association between Agent Orange and MPNs came during DoD clean-up efforts for another group of environmental contaminants—polyfluoroalkyl substances (PFAS).
PFAS refers to the entire class of approximately 600 per- and polyfluoroalkyl substances in commerce, of which perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were historically the most widely used throughout the US.
PFAS are synthetic chemicals found in many industrial and consumer products. While they are not uniquely attributable to DoD activities, DoD used aqueous film forming foam containing PFOS and PFOA in firefighting and crash response vehicle testing, fire training exercises, crash crew training exercises, hangar system operations and testing, responses to fuel fires or spills and emergency response actions. DoD also uses materials that can contain PFAS in the vapor suppression systems at plating shops.
Releases of PFAS to the environment can result from use, spills and leaks of these materials during handling or in storage, wastewater treatment and disposal locations such as landfills.3
According to the Agency for Toxic Substances and Disease Registry, the epidemiological evidence suggests associations between increases in exposure to (specific) PFAS and certain health effects including the following: increases in cholesterol levels, lower antibody response to some vaccines, changes in liver enzymes, pregnancy-induced hypertension and preeclampsia, small decreases in birth weight and kidney and testicular cancer. 4
In February, DoD released the names of more than 30 DoD installations and National Guard facilities where interim PFAS cleanup actions are underway or will start in Fiscal Year 2024. These efforts will mitigate further PFAS plume migration or ongoing impacts to groundwater from on-base PFAS source areas and build on the Biden-Harris administration’s commitments to protect public health and the environment, the department stated in a Feb. 5 press release.5
- Tiu AC, McKinnell Z, Liu S, Diao, Association of Agent Orange and myeloproliferative neoplasms, thrombosis, and bleeding among veterans. 2023 ASCO annual meeting. June 2-6, 2023. Abstr 7011. J. Clin Oncol 41, 2023 (suppl 16; abstr 7011)
- skr42. (2023, June 16). Veterans exposed to Agent Orange may be at increased risk of developing progressive blood cancers. Lombardi Comprehensive Cancer Center. https://lombardi.georgetown.edu/news-release/veterans-exposed-to-agent-orange-may-be-at-increased-risk-of-developing-progressive-blood-cancers/#
- Perfluoroalkyl and Polyfluoroalkyl Substances. Military Health System. (2023, June 20). https://www.health.mil/Military-Health-Topics/Health-Readiness/Public-Health/PFAS
- Centers for Disease Control and Prevention. (2024, Jan. 18). Potential health effects of Pfas Chemicals. Centers for Disease Control and Prevention. https://www.atsdr.cdc.gov/pfas/health-effects/index.html
- US Department of Defense. (2024, Feb. 6). DOD identifies additional locations for interim Pfas Cleanup Actions. U.S. Department of Defense. https://www.defense.gov/News/Releases/Release/Article/3668054/dod-identifies-additional-locations-for-interim-pfas-cleanup-actions/
