Background/Objectives Exome sequencing may identify pathogenic variants unrelated with the purpose of the analysis. We investigated the frequency of secondary and incidental findings (SF/IF) in cancer susceptibility genes (CSG), their clinical actionability and the psychological impact in individuals with an SF/IF (cases) compared with individuals tested due to their cancer history (controls).
Methods This study analysed 533 exomes ordered for non-cancer conditions. Medical records were reviewed for clinical actionability of SF/IF. Psychological impact was analysed using the Multidimensional Impact of Cancer Risk Assessment (MICRA) scale and compared between cases and controls with a propensity score weighting method.
Results The frequency of SF/IF in CSG was 2.1% (95% CI 1.1% to 3.8%): three BRCA2, three PMS2, two SDHB, and one each in BRCA1, MLH1 and RAD51C. Among the relatives, 18 were carriers. Twenty enrolled for surveillance, and a neoplasm was diagnosed in 20%: three paragangliomas and one breast cancer. Cases presented higher MICRA mean scores than controls (21.3 vs 16.2 in MICRA total score, 6.3 vs 4.2 in the distress subscale, and 8.3 vs 6.6 in the uncertainty subscale; all p<0.001).
Conclusion SF/IF in CSG were identified in 2.1% of patients. Despite a numerically higher psychological impact, the identification of SF/IF allowed early detection and cancer prevention in families without cancer history.
- Genetic Testing
- Genetics, Medical
- Disease Management
- Genetic Predisposition to Disease
- Genetic Counseling
Data availability statement
Data are available upon reasonable request.
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Contributors Conceptualisation: EC, JB, LM. Data curation: EC, ST-E, MC-S, IV, AMC-G, DP, AA. Formal analysis: GV, VN, EC. Funding acquisition: Not fundings. Investigation: EC, JB, LM. Methodology: EC, JB, LM, GV, VN. Project administration: EC. Resources: ST-E, MC-S, CS-A, OD, DP, MC, AMC-G, IV, BP-D, EFT, MT, EG-A, Genetica Software: ST-E, GV, VN. Supervision: JB-G, LM, EG-A, EFT. Validation: EC, JB, LM. Visualisation: EC, GV. Writing: EC, VN, GV, JB, LM, AL-F. Guarantor: EC, JB, LM. Writing review and editing: all authors.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests JB has received a speaker’s fee from AstraZeneca and Pfizer and has served AstraZeneca in an advisory role. GV has received a speaker’s fee/research honoraria from MSD and Pierre Fabre and has served AstraZeneca in an advisory role. LM is member of the data monitoring committees for clinical trials sponsored by Novartis, Actuate Therapeutics, Shionogi, Incyte, University of Southampton and Royal Marsden NHS Foundation Trust; had a consulting role for Novartis, Norgine, Boehringer, Y-mAbs and Shionogi; and participated in educational activities organised by Bayer and Eusa Pharma. LM is member of the Executive Committee of SIOPEN (European neuroblastoma research cooperative group), an organisation which receives royalties for sales of dinutuximab beta. EFT has received grant support to conduct clinical trials on SMA from Ionis/Biogen and serves as a consultant to Biogen, Novartis, AveXis, Roche, Biologix and Cytokinetics.
Provenance and peer review Not commissioned; externally peer reviewed.
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