Childhood, adolescent and young adulthood cancer risk in BRCA1 or BRCA2 pathogenic variant carriers.

Autor:	Li S; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Madanat-Harjuoja L; Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Finnish Cancer Registry, Helsinki, Finland., Leslie G; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Barnes DR; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Bolla MK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Dennis J; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Parsons MT; Public Health Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Apostolou P; Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens, Greece., Arnold N; Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany.; Institute of Clinical Molecular Biology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany., Bosse K; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany., On Behalf Of Embrace Collaborators ACA; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Cook J; Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK., Engel C; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.; LIFE-Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany., Evans DG; Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.; North West Genomics Laboratory Hub, Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Fostira F; Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens, Greece., Frone MN; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA., Gehrig A; Department of Human Genetics, University Würzburg, Würzburg, Germany., Greene MH; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA., Hackmann K; Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany., Hahnen E; Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Harbeck N; Department of Gynecology and Obstetrics, University of Munich, Campus Großhadern, Munich, Germany., Hauke J; Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Hentschel J; Institute of Human Genetics, University Hospital Leipzig, Leipzig, Germany., Horvath J; Institute of Human Genetics, University of Münster, Münster, Germany., Izatt L; Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK., Kiechle M; Department of Gynaecology and Obstetrics, University Hospital Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany., Konstantopoulou I; Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens, Greece., Lalloo F; Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK., Yie JNY; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.; Cancer Genetics Service, National Cancer Centre, Singapore., Niederacher D; Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany., Ritter J; Institute of Medical and Human Genetics, Charité -Universitätsmedizin Berlin, Berlin, Germany., Santamariña M; Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain.; Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.; Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain., Schmutzler RK; Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Searle C; Department of Clinical Genetics, Nottingham University Hospitals NHS Trust, Nottingham, UK., Sutter C; Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany., Tischkowitz M; Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.; Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montréal, QC, Canada., Tripathi V; Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK., Vega A; Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain.; Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.; Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain., Wallaschek H; Institute of Human Genetics, Hannover Medical School, Hannover, Germany., Wang-Gohrke S; Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany., Wappenschmidt B; Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Weber BHF; Institute of Human Genetics, University Regensburg, Regensberg, Germany.; Institute of Clinical Human Genetics, University Hospital Regensburg, Regensburg, Germany., Yannoukakos D; Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens, Greece., Zhao E; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Easton DF; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Antoniou AC; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Chenevix-Trench G; Cancer Research Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Rebbeck TR; Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Dana-Farber Cancer Institute, Boston, MA, USA., Diller LR; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Jazyk:	angličtina
Zdroj:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2024 Nov 25. Date of Electronic Publication: 2024 Nov 25.
DOI:	10.1093/jnci/djae306
Abstrakt:	Background: Whether carriers of BRCA1 or BRCA2 (BRCA1/2) pathogenic variants (PVs) have increased risks of childhood, adolescent, and young adult (CAYA) cancers is controversial. We aimed to evaluate this risk and to inform clinical care of young BRCA1/2 PV carriers and genetic testing for CAYA cancer patients. Methods: Using data from 47,117 individuals from 3,086 BRCA1/2 families, we conducted pedigree analysis to estimate relative risks (RRs) for cancers diagnosed before age 30. Results: Our data included 274 cancers diagnosed before age 30: 139 breast cancers, 10 ovarian cancers, and 125 non-breast non-ovarian cancers. Associations for breast cancer in young adulthood (20-29 years) were found with RRs of 11.4 (95% CI: 5.5, 23.7) and 5.2 (95% CI: 1.6, 17.7) for BRCA1 and BRCA2 PV carriers, respectively. No association was found for any other investigated CAYA cancer, nor for all non-breast non-ovarian cancers combined: the RRs were 0.4 (95% CI: 0.1, 1.4) and 1.4 (95% CI: 0.7, 3.0) in BRCA1 or BRCA2 PV carriers, respectively. Conclusion: We found no evidence that BRCA1/2 PV carriers have an increased CAYA cancer risk aside from breast cancer in women in their 20's. Our results, along with a critical evaluation of previous germline sequencing studies, suggest that the childhood and adolescent cancer risk conferred by BRCA1/2 PV would be low (ie, RR < 2) if it existed. Our findings do not support PV testing for offspring of BRCA1/2 PV carriers at ages <18 years, nor for conducting BRCA1/2 PV testing for childhood and adolescent cancer patients. (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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