OSkin Study: Genetic Risk and Nevus Count Stronger Predictors for NAM
Key Takeaways:
High nevus count and polygenic risk scores are more predictive of nevus-associated melanoma (NAM) than de novo melanoma, a recent population-based study suggests.
Sex differences were observed in anatomical distribution, but not risk factor strength, for NAM.
High nevus density and polygenic susceptibility are more strongly associated with nevus-associated melanoma (NAM) than with de novo melanoma, according to results from a new large-scale, population-based cohort study.
The QSkin Study included more than 38,000 participants aged 40 to 69, followed prospectively from 2011 to 2022. The researchers noted that it is the first of its kind to analyze risk factors for NAM versus de novo invasive melanoma, seeking to clarify how genetic and environmental contributions differ between subtypes and whether associations vary by sex. Participants self-reported phenotypic and sun exposure–related data. The authors calculated polygenic risk scores (PRS) for melanoma and nevus development. The researchers identified 859 cases of invasive melanoma over a period of more than 11 years (209 NAM and 650 de novo).
Risk factors such as lighter hair color, sun sensitivity, and history of sunburns or skin lesions were associated with both subtypes. High nevus density and elevated melanoma PRS showed stronger associations with NAM, as individuals with many moles had a higher risk [hazard ratio (HR) of 6.86 (95% CI, 3.82–12.33) for NAM vs. to 3.21 (95% CI, 2.23–4.63) for de novo melanoma (P = .001)]. Likewise, those in the highest tertile of melanoma PRS also saw elevated risk [HR of 6.46 (95% CI, 3.42–12.20) for NAM vs. 2.98 (95% CI, 2.21–4.02) for de novo melanoma (P = .006)].
No significant sex-based differences in NAM risk factors were reported. Older age was linked with a higher risk in males than in females. Males more likely to develop NAM lesions on the trunk and females on the limbs.
“Results of this study identified distinct risk factor profiles for NAM and de novo melanomas, particularly polygenic risk and nevus propensity,” the authors wrote. “Males and females tended to develop NAM on different body sites, which may have implications for early detection strategies.”
Source: Olsen C, et al. JAMA Dermatology. 2025 doi: 10.1001/jamadermatol.2025.2004