Can case-enriched melanoma data support age-specific absolute risk?

A multiple-primary melanoma series supplies affected cases, not the carrier denominator needed for penetrance. For the study indexed as PMID 41763641, what external carrier population or sampling model, if any, supports estimation of age-specific absolute risk?

Variant enrichment among cases should remain distinct from penetrance unless referral, prior testing, survival to enrollment, ancestry, and surveillance intensity are incorporated into the sampling model. A quantitative comparison of estimates under clinic-based ascertainment, inverse-probability weighting, and an unselected reference cohort would show whether any inferred risk is robust to selection. The broader modifier framework in PMID 41990334 makes the same transportability issue relevant when candidate modifiers are evaluated in this case-enriched setting.