Secondary (additional) findings from the 100,000 Genomes Project: Disease manifestation, health care outcomes, and costs of disclosure
Joshua Nolan, James Buchanan, John Taylor, João Rafael Almeida, Tina Bedenham, Edward Blair, Suzanne Broadgate, Samantha Butler, A. Cazeaux, Judith Craft, Treena Cranston, Gillian Crawford, Jamie I. Forrest, Jessica Gabriel, Elaine George, Donna Gillen, Ash Haeger, Jillian Hastings Ward, Lara Hawkes, Claire Hodgkiss, J. E. Hoffman, Alan Jones, Fredrik Karpe, Dalia Kasperavičiūtė, Erika Kovacs, S. E. A. Leigh, Elizabeth Limb, Anjali Lloyd-Jani, Javier Ferreiros, Anneke Lucassen, C J McFARLANE, Anthony W. O’Rourke, Emily Pond, Catherine Sherman, Helen Stewart, Ellen Thomas, Simon Thomas, Tessy Thomas, Kate Thomson, Hannah Wakelin, Susan Walker, Melanie Watson, Eleanor Williams, Elizabeth Ormondroyd
Abstract
PURPOSE: The UK 100,000 Genomes Project offered participants screening for additional findings (AFs) in genes associated with familial hypercholesterolemia (FH) or hereditary cancer syndromes including breast/ovarian cancer (HBOC), Lynch, familial adenomatous polyposis, MYH-associated polyposis, multiple endocrine neoplasia (MEN), and von Hippel-Lindau. Here, we report disclosure processes, manifestation of AF-related disease, outcomes, and costs. METHODS: An observational study in an area representing one-fifth of England. RESULTS: Data were collected from 89 adult AF recipients. At disclosure, among 57 recipients of a cancer-predisposition-associated AF and 32 recipients of an FH-associated AF, 35% and 88%, respectively, had personal and/or family history evidence of AF-related disease. During post-disclosure investigations, 4 cancer-AF recipients had evidence of disease, including 1 medullary thyroid cancer. Six women with an HBOC AF, 3 women with a Lynch syndrome AF, and 2 individuals with a MEN AF elected for risk-reducing surgery. New hyperlipidemia diagnoses were made in 6 FH-AF recipients and treatment (re-)initiated for 7 with prior hyperlipidemia. Generating and disclosing AFs in this region cost £1.4m; £8680 per clinically significant AF. CONCLUSION: Generation and disclosure of AFs identifies individuals with and without personal or familial evidence of disease and prompts appropriate clinical interventions. Results can inform policy toward secondary findings.