Listening to Veterans: Study Links Agent Orange Exposure to Increased Cancer Risk

Researchers from UC Irvine and the Tibor Rubin Veterans Affairs Medical Center conduct the largest study to date linking Agent Orange exposure to an increased risk for lymphatic cancer.

“The most important thing to me as a clinician researcher is to listen to my patients,” says Helen Ma, MD, a staff physician at Tibor Rubin Veterans Affairs (VA) Medical Center in Long Beach. “Their lived experiences often point us toward the most important research questions and clinical needs.”

Listening to veterans is what led Ma, also an assistant professor in the Division of Hematology and Oncology in the UC Irvine School of Medicine, to partner with the VA Medical Center on the largest study to date examining Agent Orange exposure and lymphatic cancers.

“Our motivation to perform this study came from the experiences of our patients — U.S. veterans who were exposed to Agent Orange during their service in Vietnam,” says Ma. “We heard from many veterans who raised concerns about whether Agent Orange exposure increased their risk for cancers, particularly blood cancers such as lymphoma.”

Previous research suggested exposure increased cancer risk, but this UC Irvine/VA study set out to close the gap in terms of understanding specific subtypes of cancer. The findings, outlined in a paper recently published in JAMA Network Open, reveal that Agent Orange exposure increases lymphatic cancer risk by 60% — similar to the risk for those with a genetic predisposition.

A Productive Partnership

The partnership between UC Irvine and VA Long Beach was key to this research.

“My work at the VA gives me the privilege of caring directly for veterans. I see firsthand the health challenges they face, which makes my research questions more personal and urgent,” says Ma. “At the same time, my affiliation with UC Irvine allows me access to the resources of a comprehensive cancer center. I can easily communicate with collaborators who are experts in their fields to ensure our methods in research are on the cutting edge of science.”

This knowledge and expertise helped secure the study’s funding. “UC Irvine provided the research mentorship and resources needed to generate the preliminary data that helped secure a VA research grant,” says Ma.

The research team was then able to conduct a rigorous study using data from the VA Million Veteran Program (MVP). More than 1 million veterans have joined the program, which looks at how genes, lifestyle, military experiences, and exposures affect their health and wellness.

“With access to experts at UC Irvine, we were able to design a study that combined high-quality data with a deep understanding of veterans’ health needs,” says Ma.

Exposure & Cancer Risk

Analyzing the records of more than 250,000 non-Hispanic White veterans, the researchers validated and strengthened the link between Agent Orange exposure and lymphoid malignancies. Their findings provide additional information related to the estimated risk for each subtype: chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma and multiple myeloma.

Furthermore, this is the only study to investigate both Agent Orange exposure as well as gene association, noting that the risk was not higher in individuals with both toxic exposure and genetic predisposition.

The findings could lead to research in other areas as well. “Beyond Agent Orange, the study highlights how environmental exposures can be associated with cancer risk,” says Ma, “a lesson that can inform research related to exposures such as other carcinogens, burn pits and wildfires.”

Continued Collaboration

VA has a long history of partnering with academic institutions to support healthcare for veterans and the nation at large. “This collaboration starts with VA providing a portion of medical education to roughly 70% of physicians in the United States, and it continues through close research collaboration with established academic researchers,” says Stephen Dagadakis, a public affairs officer with VA Long Beach. “MVP is a perfect example of the promise — and impact — of VA’s research collaboration.” In addition to knowledge gained from the partnership between UC Irvine and VA, he notes how MVP data has been used by over 250 researchers from more than 75 academic institutions, advancing knowledge of chronic diseases, including anxiety, PTSD, depression, heart disease and kidney disease.

Ma is grateful for the continued collaboration. “Clinical care helps me design studies that are grounded in the real needs of patients,” she says. “VA also has resources such as the MVP, comprehensive medical records and statistical software to perform the analyses.” Research partnerships help ensure veterans get the best possible care based on scientific evidence.

“Ongoing research is essential,” says Ma. “We owe it to our veterans to continue seeking answers about the long-term effects of their service, and to turn that knowledge into better health and quality of life.”