Study Links Agent Orange Exposure to Acral Melanoma in Veterans

As Veterans Day brings renewed attention to the long-term health needs of US military veterans, findings published in JAMA Dermatology highlight a potential association between Agent Orange exposure and acral melanoma, a rare melanoma subtype that develops on the palms, soles, and nail units.

The study, "Identification of Risk Factors for Acral Melanoma in US Veterans," identified significantly higher odds of acral melanoma among veterans with documented Agent Orange exposure compared with veterans diagnosed with nonacral cutaneous melanoma and those without melanoma. The findings underscore the importance of understanding melanoma risk factors beyond ultraviolet (UV) radiation, particularly among individuals with a history of military-related environmental exposures.

“Researchers are still learning about why acral melanoma develops and its risk factors,” — Jessica Scales, PhD, associate director of rare melanoma research at the Melanoma Research Alliance (MRA).

Examining Acral Melanoma Risk in Veterans

Researchers conducted a nested case-control study using Veterans Affairs (VA) health care system data collected between 2000 and 2024. The analysis included 1292 veterans with histologically confirmed acral melanoma, matched with controls who had nonacral cutaneous melanoma or no melanoma diagnosis.

Acral melanoma differs from more common forms of cutaneous melanoma because it is less strongly associated with UV exposure. Its development remains poorly understood, making the identification of potential environmental and clinical risk factors particularly important.

Researchers evaluated several characteristics, including age, sex, race and ethnicity, military branch, smoking status, comorbidities, previous dermatologic conditions, and documented Agent Orange exposure.

The analysis found that Agent Orange exposure was associated with 31% higher adjusted odds of acral melanoma compared with nonacral cutaneous melanoma (adjusted odds ratio [aOR], 1.31; 95% CI, 1.06-1.62). Compared with veterans without melanoma, the association remained significant, with 27% higher adjusted odds (aOR, 1.27; 95% CI, 1.04-1.56).

These findings suggest a potential relationship between Agent Orange exposure and acral melanoma, although the observational study does not establish a causal association.

Understanding the Importance of Early Detection

The findings also align with broader efforts to improve awareness and detection of rare melanoma subtypes.

In a recent Dermatology Times interview, Jessica Scales, PhD, associate director of Rare Melanoma Research at the Melanoma Research Alliance, discussed the organization's RARE Registry and the importance of identifying acral melanoma during routine dermatologic examinations.

"Dermatologists are actually uniquely positioned to monitor these sites during routine skin screenings," Scales said.

According to Scales, patients with acral melanoma participating in the registry reported initial symptoms including new or changing moles, nail streaks, bleeding, and nonhealing wounds. The soles of the feet were the most frequently reported sites, followed by locations beneath the toenails or fingernails.

Unlike melanoma typically associated with sun exposure, acral melanoma can develop in areas that may be overlooked during routine skin examinations. It can also affect individuals across racial and ethnic populations.

Implications for Dermatologic Care

The study identified additional factors associated with acral melanoma, including previous nevi, keratinocyte carcinoma, and actinic keratosis in comparisons with veterans without melanoma. However, associations varied depending on the comparison group, reinforcing the complexity of acral melanoma risk.

Although current smoking was associated with lower odds of acral melanoma in the analysis, this observational finding should not be interpreted as evidence of a protective effect or a reason to alter smoking-related clinical recommendations.

For dermatologists caring for veterans, the findings reinforce the potential value of considering military exposure history alongside conventional dermatologic risk assessments. They also highlight the importance of examining acral sites and evaluating suspicious lesions, particularly those involving changing pigmentation, nail abnormalities, or persistent wounds.

As researchers continue to investigate the biological and environmental factors associated with rare melanoma subtypes, the study provides a foundation for further examination of Agent Orange exposure and acral melanoma.

This Veterans Day, the findings offer an opportunity to recognize the importance of continued research into the long-term health consequences of military service and the role dermatologists can play in identifying potentially serious skin conditions.

References

1. 1. Identification of risk factors for acral melanoma in US veterans. JAMA Dermatol. 2026. doi:10.1001/jamadermatol.2025.5827. https://pubmed.ncbi.nlm.nih.gov/41637103/
2. Scales J. MRA's RARE Registry data report findings on acral and mucosal melanoma. Dermatology Times. 2026. https://www.dermatologytimes.com/view/mra-s-rare-registry-data-report-findings-on-acral-and-mucosal-melanoma
3. Scales J. The RARE Registry 2026 Data Report: Patient Voices Empowering Research. Melanoma Research Alliance. Published July 30, 2026. https://www.curemelanoma.org/blog/the-rare-registry-2026-data-report-patient-voices-empowering-research