Clinical outcomes of a genomic screening program for actionable genetic conditions

TLDR

Hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia have tier‑1 evidence that interventions can reduce morbidity and mortality, motivating proposals for population screening. We examined the impact of genomic screening on risk management and early detection in an unselected population. We conducted an observational EHR study of individuals with pathogenic variants identified via Geisinger’s MyCode project, assessing prior diagnoses, family history, post‑disclosure clinical outcomes, and risk‑management actions. Among 351 participants, 87% lacked a prior genetic diagnosis, 65% had evidence of relevant personal or family history, 70% of those eligible received recommended risk‑management procedures, 13% obtained a new clinical diagnosis, and the program effectively identified previously unrecognized high‑risk individuals and promoted early detection.

Abstract

Three genetic conditions—hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia—have tier 1 evidence for interventions that reduce morbidity and mortality, prompting proposals to screen unselected populations for these conditions. We examined the impact of genomic screening on risk management and early detection in an unselected population. Observational study of electronic health records (EHR) among individuals in whom a pathogenic/likely pathogenic variant in a tier 1 gene was discovered through Geisinger’s MyCode project. EHR of all eligible participants was evaluated for a prior genetic diagnosis and, among participants without such a diagnosis, relevant personal/family history, postdisclosure clinical diagnoses, and postdisclosure risk management. Eighty-seven percent of participants (305/351) did not have a prior genetic diagnosis of their tier 1 result. Of these, 65% had EHR evidence of relevant personal and/or family history of disease. Of 255 individuals eligible to have risk management, 70% (n = 179) had a recommended risk management procedure after results disclosure. Thirteen percent of participants (41/305) received a relevant clinical diagnosis after results disclosure. Genomic screening programs can identify previously unrecognized individuals at increased risk of cancer and heart disease and facilitate risk management and early cancer detection.