A population-based study using information from a database of veterans found that those who had been exposed to Agent Orange may be at an increased risk of developing myeloproliferative neoplasms (MPNs). Agent Orange is a herbicide that was used by the U.S. military in Korea and Vietnam to clear foliage during combat. It has been associated with an increased risk of developing sarcomas and B-cell lymphomas but not MPNs or leukemias to date. These findings were presented by Tiu et al at the 2023 ASCO Annual Meeting (Abstract 7011).
“MPNs are associated with serious cardiovascular events, and people with this disease have decreased overall survival chances,” explained lead study author Andrew Tiu, MD, a second-year hematology/oncology fellow with Medstar Georgetown University Hospital who also conducts research at Georgetown University’s Lombardi Comprehensive Cancer Center. “But until now, we haven’t been able to fully ascertain whether Agent Orange exposure truly leads to the development of MPNs, which is why we’ve undertaken what is the biggest population-based study to date to try to answer this question.”
Study Details
To explore associations between Agent Orange and MPNs, in addition to risks of blood clots, bleeding, and a number of cardiovascular disease risk factors associated with the herbicide, the researchers used the Veterans Affairs Informatics and Computing Infrastructure (VINCI) database. They examined records of 93,269 patients with MPNs among 12,352,664 veterans over 17 years. The researchers included veterans from the state of Illinois as a control population, since Illinois is highly representative of the United States, according to the U.S. Census Bureau.
Significant findings from the study include the following:
- The odds of Agent Orange exposure among patients with MPNs were 1.63 times greater than the odds of exposure among controls.
- When comparing people with MPNs vs age-, gender-, and race-matched controls, there was more clotting in the arteries (37% vs 18.5%), more clotting in the veins (14.8% vs 5.2%), and more bleeding events (39.1% vs 13.5%), respectively, in the patients with MPNs.
- 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.
Because the team’s findings only point to possible associations and not causes, Dr. Tiu noted that the researchers will need to dive more deeply into the biology of MPNs. Specifically, they want to look at JAK2 mutations, which are one of the three driver mutations linked to MPNs (the other two being MPL and CALR mutations) that may cause uncontrolled proliferation of stem cells. JAK2 mutations have also been associated with an increased risk of clotting.
“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 Dr. Tiu. “We are proud of the fact that our work was selected for a 2023 Conquer Cancer Merit Award, and we’ll be using those funds to further our research efforts.”
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
