“Noteworthy” Link Between Agent Orange and Acral Melanoma Found

Recent research has revealed potential links between Agent Orange (AO) exposure and risk of acral melanoma (AM) among Vietnam War-era veterans, providing strong evidence of a relationship between the chemical and this type of cancer.

Localized to the palms, soles, and nail units, AM is a melanoma subtype less associated with UV radiation. From 1962 to 1971, the US military sprayed an estimated 18 million gallons of herbicides, including AO, over the fields and forests of Vietnam. Those herbicides have since been connected to numerous health issues, including cancer, though evidence of a relationship between AO and skin cancers has been weak. 

Vietnam War-era veterans have a higher melanoma burden than the general population, with the disease being the fourth-most common cancer among those who served. AM, however, is rare, representing about 2% to 3% of all melanomas. 

In a nested case-control study, Hwang et al used US Department of Veterans Affairs (VA) health care system data, including the VA Cancer Registry. The authors compared 1292 patients with AM and 2 pair-matched control groups: a group matched 4:1 to nonacral cutaneous melanoma controls, and a group without a melanoma diagnosis. 

Hwang et al found AO exposure was associated with increased odds of AM compared with each control group. In an accompanying editorial, Andrew Olshan, PhD, from Department of Epidemiology at the University of North Carolina Gillings School of Global Public Health, wrote, “The magnitude of the effects was modest (about 30%) but noteworthy.” 

A limitation of the study was that presumptive AOE status was based on whether the veteran filed a disability claim with evidence of officially recognized service in a period and place where Agent Orange was used—not on an assessment of the veteran’s individual AOE potential, including level of exposure. Because melanoma has never been included on the VA list of cancers presumed to be related to AO exposure, veterans do not automatically gain benefits by filing AOE claims after diagnosis. Even so, Olshan says, the reported study findings may underestimate the true effect of AO exposure on the risk of AM. 

Given the rarity of AM, the association (if causal) would translate to 0.4 to 0.8 new annual cases of AM per 1,000,000 veterans, according to the study. Narrowed down to Vietnam War-era veterans—who are dwindling in number—the attributable cases would be scarce.

Nevertheless, the search for a better understanding of a potential link between AOE and melanomas among Vietnam War-era veterans is important, Olshan wrote.

“The Hwang et al study provides a strong impetus to further these research goals and contribute to the investigation of the legacy of the Vietnam War and honor a commitment to the veterans community.”