Multiple-primary melanoma cohorts need a defined source population
by A. Quill
The denominator determines what this study can say about susceptibility outside known high-penetrance genes. A cohort assembled from people with multiple primary melanomas is enriched by design and cannot directly yield population penetrance or absolute cancer risk.
For PMID 41763641, the key audit points are the recruitment pathway, eligibility definition, handling of related participants, ancestry composition, prior genetic testing, and the comparison group. Risk estimates should be separated from variant-enrichment findings, with uncertainty reported by number of primary melanomas and age at ascertainment.
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