Age-specific melanoma risk associated with nevi: a pooled analysis from the M-SKIP project

Objective: This study investigates the association of melanoma risk with total-body nevus count and the presence of atypical nevi in younger (< 40 years) and older (> 60 years) individuals. Methods: A pooled analysis was conducted within the M-SKIP project, based on multiple melanoma case-control studies. Associations were assessed through study-specific odds ratios (ORs), adjusted for potential confounders. Results: Nine case-control studies were included, analyzing common nevi (2,674 melanoma cases/2,343 controls) and atypical nevi (2,459 cases/1,740 controls). High common nevus count was associated with increased melanoma risk in both younger (summary [s]OR = 2.56; 95% CI 1.64-4.01; I2 = 31%) and older individuals (sOR = 2.06; 95% CI 1.06–4.00; I2 = 67%), with no significant age-group difference (p = 0.57). In contrast, younger individuals exhibited a markedly higher risk of melanoma associated with the presence of at least one atypical nevus (sOR = 4.84, 95% CI 2.18–10.76; I2 = 65%) compared to older individuals (sOR = 1.71 95%CI 1.07–2.74; I2 = 39%), with a p value for the difference of 0.02. Conclusions: These findings suggest age-specific differences in melanoma risk associated with nevus burden. Specifically, atypical nevi are a stronger risk factor in younger individuals. This could have significant implications for prevention strategies and clinical management, in particular for better identification of high-risk groups for targeted secondary prevention efforts.