Analysis: Agent Orange Exposure Linked to Acral Melanoma Risk in US Veterans
Key Takeaways
A new analysis suggests Agent Orange exposure (AOE) was associated with higher odds of acral melanoma compared with both nonacral melanoma and no melanoma.
Traditional UV-related markers like actinic keratosis and keratinocyte carcinoma were shown to have associations when acral melanoma was compared with cutaneous melanoma.
Acral melanoma may be a biologically and epidemiologically distinct melanoma subtype in US veterans, according to the researchers.
Acral melanoma (AM), a rare melanoma subtype, showed risk factor patterns in a large Veterans Affairs (VA)–based analysis spanning more than two decades, according to new data.
In this case-control study of US veterans from 2000 to 2024, investigators evaluated demographic, clinical, and environmental exposures associated with AM, comparing cases with both nonacral cutaneous melanoma (CM) controls and controls without any melanoma diagnosis. The analysis included 1,292 veterans with histologically confirmed AM who were predominantly older and male. Each case was matched by diagnosis year and outpatient visit frequency to both CM controls and melanoma-free controls. The authors identified Agent Orange exposure (AOE) as a significant risk factor for AM. AOE was associated with higher odds of AM compared with CM (AOR = 1.31; 95% CI, 1.06 to 1.62) and compared with controls without melanoma (AOR = 1.27; 95% CI, 1.04 to 1.56).
Current smoking status was consistently associated with lower odds of AM across both comparator groups, as a contrast, which the investigators noted should be interpreted cautiously. Prior keratinocyte carcinoma and actinic keratosis were linked to higher odds of AM relative to melanoma-free controls but lower odds when AM was compared with CM. A history of nevi was associated with increased odds of AM compared with controls without melanoma.
"Results of this study suggest that several factors were associated with AM in veterans and a need for continued investigation of AM as a distinct entity from CM and may inform future evaluations of the associations between AOE and AM in veteran populations," the authors concluded.
An accompnying editorial noted the ongoing fallout of the exposure, noting "[t]he legacy of AOE and health effects for U.S. Vietnam veterans and the citizens of Vietnam has been long and concerns linger to this day."
Sources:
Hwang J, et al. JAMA Dermatology. 2026. doi:10.1001/jamadermatol.2025.5827
Olshan A. JAMA Dermatology.2026. doi:10.1001/jamadermatol.2025.5771