Clinical and psychological implications of secondary and incidental findings in cancer susceptibility genes after exome sequencing in patients with rare disorders.

Autor:	Carrasco E; Hereditary Cancer Genetics Group, Medical Oncology Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Department of Pediatrics, Obstetrics and Gynecology, Preventative Medicine and Public Health, Autonomous University of Barcelona, Barcelona, Spain.; Hereditary Cancer Genetics Group, Medical oncology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035, Barcelona, Spain., López-Fernández A; Hereditary Cancer Genetics Group, Medical Oncology Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Hereditary Cancer Genetics Group, Medical oncology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035, Barcelona, Spain., Codina-Sola M; Department of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Medicine Genetics Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA [EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516], ERN-ITHACA, Barcelona, Spain., Valenzuela I; Department of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Medicine Genetics Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA [EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516], ERN-ITHACA, Barcelona, Spain., Cueto-González AM; Department of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Medicine Genetics Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA [EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516], ERN-ITHACA, Barcelona, Spain., Villacampa G; Oncology Data Science (ODysSey) Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035, Barcelona, Spain., Navarro V; Oncology Data Science (ODysSey) Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035, Barcelona, Spain., Torres-Esquius S; Hereditary Cancer Genetics Group, Medical oncology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035, Barcelona, Spain., Palau D; Department of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA [EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516], ERN-ITHACA, Barcelona, Spain., Cruellas M; Hereditary Cancer Genetics Group, Medical Oncology Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Hereditary Cancer Genetics Group, Medical oncology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035, Barcelona, Spain., Torres M; Hereditary Cancer Genetics Group, Medical Oncology Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain., Perez-Dueñas B; Paediatric Neurology Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035 Universitat Autónoma de Barcelona, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain., Abulí A; Department of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Medicine Genetics Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA [EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516], ERN-ITHACA, Barcelona, Spain., Diez O; Hereditary Cancer Genetics Group, Medical oncology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035, Barcelona, Spain.; Department of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA [EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516], ERN-ITHACA, Barcelona, Spain., Sábado-Álvarez C; Department of Pediatric Oncology and Hematology, Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035, Barcelona, Spain., García-Arumí E; Department of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Medicine Genetics Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA [EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516], ERN-ITHACA, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.; Research Group on Neuromuscular and Mitochondrial Disorders, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain., Tizzano EF; Department of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Medicine Genetics Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA [EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516], ERN-ITHACA, Barcelona, Spain., Moreno L; Department of Pediatric Oncology and Hematology, Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035, Barcelona, Spain lucas.moreno@vallhebron.cat.; Childhood Cancer and Blood Disorders Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain., Balmaña J; Hereditary Cancer Genetics Group, Medical Oncology Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Hereditary Cancer Genetics Group, Medical oncology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035, Barcelona, Spain.; Member of the European Reference Network on GENTURIS, ID: HP-ERN-2016 739547, GENTURIS, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2023 Jul; Vol. 60 (7), pp. 685-691. Date of Electronic Publication: 2022 Nov 29.
DOI:	10.1136/jmg-2022-108929
Abstrakt:	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. Competing Interests: 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. (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu