Opportunistic genomic screening has clinical utility: An interventional cohort study

Chloe Mighton¹, Rita Kodida², Salma Shickh¹, Marc Clausen², Emma Reble², Jordan Sam², Sonya Grewal², Daena Hirjikaka², Seema Panchal³, Carolyn Piccinin³, Melyssa Aronson⁴, Thomas Ward⁵, Susan Randall Armel⁶, Renee Hofstedter⁷, Tracy Graham⁸, Talia Mancuso⁹, Nicole Forster¹⁰, José-Mario Capo-Chichi¹¹, Elena Greenfeld¹², Abdul Noor¹², Iris Cohn¹³, Chantal F Morel¹⁴, Christine Elser¹⁵, Andrea Eisen⁹, June C Carroll¹⁶, Emily Glogowksi¹⁷, Kasmintan A Schrader¹⁸, Kelvin K W Chan¹⁹, Kevin E Thorpe²⁰, Jordan Lerner-Ellis¹², Raymond H Kim²¹, Yvonne Bombard²²; Incidental Genomics Study Team

Collaborators, Affiliations

Collaborators

Affiliations

¹ Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, ON, Canada; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
² Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
³ The Marvelle Koffler Breast Centre, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
⁴ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
⁵ Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
⁶ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, Toronto, ON, Canada.
⁷ Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, Toronto, ON, Canada.
⁸ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
⁹ Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
¹⁰ Fred A. Litwin Family Centre in Genetic Medicine, University Health Network, Toronto, ON, Canada.
¹¹ Genome Diagnostics Division, Toronto General Hospital, University Health Network, Toronto, ON, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
¹² Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Pathology and Laboratory Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
¹³ Division of Clinical Pharmacology & Toxicology, Hospital for Sick Children, Toronto, ON, Canada.
¹⁴ Fred A. Litwin Family Centre in Genetic Medicine, University Health Network, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁵ The Marvelle Koffler Breast Centre, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁶ Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada; Granovsky Gluskin Family Medicine Centre, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
¹⁷ Sanofi Genzyme, New York, NY.
¹⁸ Hereditary Cancer Program, BC Cancer, Vancouver, BC, Canada; Department of Medical Genetics, The University of British Columbia, Vancouver, BC, Canada.
¹⁹ Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, ON, Canada; Division of Medical Oncology and Hematology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²⁰ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
²¹ Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, Toronto, ON, Canada; Fred A. Litwin Family Centre in Genetic Medicine, University Health Network, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Division of Medical Oncology and Hematology, Princess Margaret Hospital Cancer Centre, Toronto, ON, Canada. Electronic address: raymond.kim@uhn.ca.
²² Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, ON, Canada; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada. Electronic address: yvonne.bombard@utoronto.ca.

PMID: 39530317
PMCID: PMC12257567 (available on 2026-02-01)
DOI: 10.1016/j.gim.2024.101323

Opportunistic genomic screening has clinical utility: An interventional cohort study

Chloe Mighton et al. Genet Med. 2025 Feb.

. 2025 Feb;27(2):101323.

doi: 10.1016/j.gim.2024.101323. Epub 2024 Nov 9.

Authors

Collaborators

Affiliations

¹ Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, ON, Canada; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
² Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
³ The Marvelle Koffler Breast Centre, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
⁴ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
⁵ Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
⁶ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, Toronto, ON, Canada.
⁷ Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, Toronto, ON, Canada.
⁸ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
⁹ Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
¹⁰ Fred A. Litwin Family Centre in Genetic Medicine, University Health Network, Toronto, ON, Canada.
¹¹ Genome Diagnostics Division, Toronto General Hospital, University Health Network, Toronto, ON, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
¹² Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Pathology and Laboratory Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
¹³ Division of Clinical Pharmacology & Toxicology, Hospital for Sick Children, Toronto, ON, Canada.
¹⁴ Fred A. Litwin Family Centre in Genetic Medicine, University Health Network, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁵ The Marvelle Koffler Breast Centre, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁶ Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada; Granovsky Gluskin Family Medicine Centre, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
¹⁷ Sanofi Genzyme, New York, NY.
¹⁸ Hereditary Cancer Program, BC Cancer, Vancouver, BC, Canada; Department of Medical Genetics, The University of British Columbia, Vancouver, BC, Canada.
¹⁹ Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, ON, Canada; Division of Medical Oncology and Hematology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²⁰ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
²¹ Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, Toronto, ON, Canada; Fred A. Litwin Family Centre in Genetic Medicine, University Health Network, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Division of Medical Oncology and Hematology, Princess Margaret Hospital Cancer Centre, Toronto, ON, Canada. Electronic address: raymond.kim@uhn.ca.
²² Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, ON, Canada; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada. Electronic address: yvonne.bombard@utoronto.ca.

PMID: 39530317
PMCID: PMC12257567 (available on 2026-02-01)
DOI: 10.1016/j.gim.2024.101323

Abstract

Purpose: Practice is shifting toward genome-first approaches, such as opportunistic screening for secondary findings (SFs). Analysis of SFs could be extended beyond medically actionable results to include non-medically actionable monogenic disease risks, carrier status, pharmacogenomic variants, and risk variants for common complex disease. However, evidence on the clinical utility of returning these results is lacking. We assessed the outcomes of opportunistic screening for a broad spectrum of SFs by evaluating the yield, impact on clinical management, and consistency between SFs and participants' clinical features and family history.

Methods: Adult cancer patients had exome sequencing with the option to learn multiple categories of SFs. Outcomes data were collected through chart review and participant-reported measures up to one year after return of results.

Results: All participants (n = 139, 85.6% female, average 54.6 years old) who elected to learn SFs had ≥1 variant reported (100% [139/139]). The yield of reportable findings was highest for pharmacogenomic variants (97.8% [135/138] of participants), followed by common disease risk variants (89.4% [118/132]), carrier status (89.3% [117/131]), and variants related to Mendelian (27.2% [34/125]), medically actionable (15.2% [21/138]), and early-onset neurodegenerative (2.6% [3/117]) disease risks. SFs from the American College of Medical Genetics and Genomics list (v3.2, noncancer genes) were reported in 1.4% (2/138) of participants. SFs across all categories demonstrated clinical utility by prompting management changes in 28.1% (39/139) of participants. Moreover, a considerable proportion of participants had suggestive clinical features (49.0% (24/49)]) or family history (21.8% (27/124)) potentially related to their SFs.

Conclusion: Our findings indicate there are potential benefits from opportunistic screening for a broad range of SFs.

Keywords: Clinical utility; Genomic screening; Secondary findings.

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Conflict of interest statement

Conflict of Interest Yvonne Bombard holds ownership stake of Genetics Adviser, Inc as CEO and cofounder.

References

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Opportunistic genomic screening has clinical utility: An interventional cohort study

Collaborators

Affiliations

Opportunistic genomic screening has clinical utility: An interventional cohort study

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical