Identification of Risk Factors for Acral Melanoma in US Veterans

Acral melanoma (AM), localized to the palms, soles, and nail units, is a unique melanoma subtype less associated with UV radiation. Few studies have evaluated AM risk factors in a population of US veterans.

To identify AM risk factors in US veterans.

Nested case-control study (2000-2024) in the Veterans Affairs (VA) health care system. Individuals with AM were identified using the VA Cancer Registry and a validated natural language processing pipeline applied to pathology reports. Each AM case was matched to 4 nonacral cutaneous melanoma (CM) controls and 4 controls with no melanoma diagnoses at any time by diagnosis year and outpatient visit frequency. Controls with acral, mucosal, or ocular melanoma diagnoses at any time were excluded. Participants were veterans with histologically confirmed AM, nonacral CM controls, and controls with no melanoma diagnoses at any time.

Age, sex, race and ethnicity, rurality, region, military branch, comorbidities (National Cancer Institute Comorbidity Index), smoking status, unhealthy alcohol use as measured by the Alcohol Use Disorders Identification Test-Consumption, body mass index, Agent Orange exposure (AOE), prior photosensitizing medications, nevi, keratinocyte carcinoma (KC), actinic keratosis (AK), and number of dermatology visits in the 2 years before diagnosis.

Adjusted odds ratios (AORs) comparing AM with controls using conditional logistic regression. Secondary outcomes included analyses limited to Vietnam Era veterans and AM localized to palmoplantar and subungual sites.

In total, 1292 individuals with AM (median age, 70.13 [IQR, 61.87-78.66] years; 1215 [94.0%] male) were matched to 5168 controls without melanoma (median age, 73.97 [IQR, 65.53-82.08] years; 5044 [97.6%] male), and 1286 individuals with AM (median age, 70.13 [IQR, 61.97-78.67] years; 1210 [94.1%] male) were matched to 5144 CM controls (median age, 74.58 [IQR, 66.86-82.05] years; 5068 [98.5%] male); 6 individuals with AM were excluded from AM vs CM analyses due to lack of matches. AOE was significantly associated with higher odds of AM vs CM (AOR, 1.31; 95% CI, 1.06-1.62) and vs controls without melanoma (AOR, 1.27; 95% CI, 1.04-1.56). Current smoking was associated with lower odds of AM (vs CM: AOR, 0.65; 95% CI, 0.52-0.81; vs controls without melanoma: AOR, 0.50; 95% CI, 0.40-0.62). Prior KC and AK were associated with higher odds vs controls without melanoma but lower odds vs CM. Prior nevus was associated with higher odds of AM vs 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.