Clinical and psychological implications of secondary and incidental findings in cancer susceptibility genes after exome sequencing in patients with rare disorders
Carrasco, Estela (Universitat Autònoma de Barcelona)
López-Fernández, Adrià (Hospital Universitari Vall d'Hebron)
Codina Solà, Marta (Hospital Universitari Vall d'Hebron)
Valenzuela, Irene (Hospital Universitari Vall d'Hebron)
Cueto-González, Anna Mª (Hospital Universitari Vall d'Hebron)
Villacampa Javierre, Guillermo (Vall d'Hebron Institut d'Oncologia)
Navarro Garcés, Víctor (Vall d'Hebron Institut d'Oncologia)
Torres Esquius, Sara (Vall d'Hebron Institut d'Oncologia)
Palau-Sampio, Dolors (Hospital Universitari Vall d'Hebron)
Cruellas, Mara (Hospital Universitari Vall d'Hebron)
Torres, Maite (Hospital Universitari Vall d'Hebron)
Pérez-Dueñas, Belén (Hospital Universitari Vall d'Hebron)
Abulí, Anna (Hospital Universitari Vall d'Hebron)
Diez, Orland (Hospital Universitari Vall d'Hebron)
Sábado, Constantino (Hospital Universitari Vall d'Hebron)
García Arumí, Elena (Hospital Universitari Vall d'Hebron)
Tizzano, Eduardo F. (Hospital Universitari Vall d'Hebron)
Moreno Martin Retortillo, Lucas (Hospital Universitari Vall d'Hebron)
Balmaña Gelpí, Judith (Hospital Universitari Vall d'Hebron)

Data:	2023
Resum:	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.
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Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Disease Management ; Genetic Counseling ; Genetic Predisposition to Disease ; Genetic Testing ; Genetics ; Medical
Publicat a:	Journal of medical genetics, Vol. 60, Num. 7 (July 2023) , p. 685-691, ISSN 1468-6244

DOI: 10.1136/jmg-2022-108929

Postprint 39 p, 3.4 MB

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