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Observational Study
. 2020 Nov;22(11):1874-1882.
doi: 10.1038/s41436-020-0876-4. Epub 2020 Jun 30.

Clinical outcomes of a genomic screening program for actionable genetic conditions

Adam H Buchanan  1 , H Lester Kirchner  2 , Marci L B Schwartz  3 , Melissa A Kelly  3 , Tara Schmidlen  3 , Laney K Jones  3 , Miranda L G Hallquist  3 , Heather Rocha  3 , Megan Betts  3 , Rachel Schwiter  3 , Loren Butry  3 , Amanda L Lazzeri  3 , Lauren R Frisbie  3 , Alanna Kulchak Rahm  3 , Jing Hao  3   2 , Huntington F Willard  3   4 , Christa L Martin  3   5 , David H Ledbetter  3   5 , Marc S Williams  3 , Amy C Sturm  3
Affiliations
Observational Study

Clinical outcomes of a genomic screening program for actionable genetic conditions

Adam H Buchanan et al. Genet Med. 2020 Nov.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: Genomic screening programs can identify previously unrecognized individuals at increased risk of cancer and heart disease and facilitate risk management and early cancer detection.

Keywords: BRCA1; BRCA2; Lynch syndrome; familial hypercholesterolemia; genomic screening.

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Conflict of interest statement

None of the authors has a financial relationship with Regeneron Genetics Center. A.H.B.’s work has been funded by the National Institutes of Health (NIH) and the Marcus Foundation. He has received compensation as a section editor for the Journal of Genetic Counseling. He holds an equity stake in MeTree and You, Inc. L.K.’s work has been funded by the NIH, Patient-Centered Outcomes Research Institute (PCORI), and the Geisinger Health Plan Quality Fund. The work of M.L.B.S., M.A.K., T.S., M.L.G.H., M.B., L.B., A.L.L., L.K.J., A.K.R., and A.C.S. has been funded by the NIH. J.H.’s work has been funded by the NIH, Geisinger Health Plan, and Progenity, Inc. H.F.W. receives compensation as a member of the scientific advisory boards of the Simons Foundation and Helix. He previously received compensation as a member of the scientific review board of the Howard Hughes Medical Institute. C.L.M.’s work has been funded by the NIH and Simons Foundation. Dr. Ledbetter’s work has been funded by the NIH and the Marcus Foundation. He has received stock options as a scientific consultant to Clear Genetics, Natera and X-Therma. M.S.W.’s work has been funded by the NIH. He receives royalties from Elsevier. L.R.F., R.S., and H.R. declare no conflicts of interest.

Figures

Fig. 1
Fig. 1. Relevant personal and family history among participants without prior genetic diagnosis.
a Relevant personal and family history in cohort. b Relevant personal and family history by genetic condition. FH familial hypercholesterolemia, HBOC hereditary breast and ovarian cancer syndrome, Hx history.
See this image and copyright information in PMC

References

    1. Manickam K, Buchanan AH, Schwartz MLB, et al. Exome sequencing-based screening for BRCA1/2 expected pathogenic variants among adult biobank participants. JAMA Netw Open. 2018;1:e182140. - PMC - PubMed
    1. Gabai-Kapara E, Lahad A, Kaufman B, et al. Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2. Proc Natl Acad Sci U S A. 2014;111:14205–14210. - PMC - PubMed
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    1. Buchanan AH, Manickam K, Meyer MN, et al. Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants. Genet Med. 2018;20:554–558. - PMC - PubMed
    1. Jones LK, Kulchak Rahm A, Manickam K, et al. Healthcare utilization and patients’ perspectives after receiving a positive genetic test for familial hypercholesterolemia. Circ Genom Precis Med. 2018;11:e002146. - PubMed

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