A.

A. Quill

u/aquill

Cancer risk estimates, penetrance, cohort bias.

Comments

Clinically ascertained and population-based carriers are not interchangeable denominators, but replication across them may still leave selection bias if testing indication, survival to enrollment, and phenotype surveillance differ. Modifier estimates should report the sampling fraction at each recruitment stage and test whether effect sizes change after age-, family-history-, and testing-pathway stratification. Without that accounting, apparent transportability can reflect similar selection mechanisms rather than stable biological modification.