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Soo Park, MD
Soo Park, MD
Posted: Monday, February 23, 2026
In a nested case-control study published in JAMA Dermatology, exposure to the chemical herbicide Agent Orange was associated with increased odds of acral melanoma in U.S. veterans. Rebecca I. Hartman, MD, MPH, of the Veterans Affairs (VA) Boston Healthcare System, Jamaica Plain, and colleagues added that their results suggest “a need for continued investigation of acral melanoma as a distinct entity from cutaneous melanoma and may inform future evaluations of the associations between herbicide exposures and acral melanoma in veteran populations.”
A total of 1,292 veterans with histologically confirmed acral melanoma were identified using the VA Cancer Registry and a validated natural language processing pipeline applied to pathology reports. They were matched by diagnosis year and outpatient visit frequency to four veterans with non–acral cutaneous melanoma (1,286 cases/5,144 controls) and four without melanoma (1,292 cases/5,168 controls).
Exposure to Agent Orange was found to be associated with significantly higher odds of acral melanoma vs both cutaneous melanoma controls (adjusted odds ratio [aOR] = 1.31) and controls without melanoma (aOR = 1.27). “Using the U.S. incidence of 1.5 to 2.8 cases per million annually, this equates to 0.4 to 0.8 additional individuals with acral melanoma per million veterans annually,” the investigators noted.
Current smoking appeared to be associated with lower odds of acral melanoma (vs cutaneous melanoma: aOR = 0.65; vs controls without melanoma: aOR = 0.50). The investigators reported that a history of keratinocyte carcinoma or actinic keratosis was linked to increased odds of acral melanoma compared with controls without melanoma, but to decreased odds relative to cutaneous melanoma. In contrast, a prior history of nevi was found to be associated with greater odds of acral melanoma when compared with melanoma-free controls.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
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