Ovarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D.

Autor:	Yang X; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Song H; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Leslie G; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Engel C; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany., Hahnen E; Faculty of Medicine and University Hospital Cologne, Center for Familial Breast and Ovarian Cancer, University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, University of Cologne, Cologne, Germany., Auber B; Institute of Human Genetics, Hannover Medical School, Hannover, Germany., Horváth J; Institute of Human Genetics, University of Münster, Münster, Germany., Kast K; Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.; German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany., Niederacher D; Department of Gynecology and Obstetrics, Heinrich-Heine University Düsseldorf, University Hospital Düsseldorf, Düsseldorf, Germany., Turnbull C; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Houlston R; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Hanson H; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Loveday C; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Dolinsky JS; Ambry Genetics, Aliso Viejo, Canada., LaDuca H; Ambry Genetics, Aliso Viejo, Canada., Ramus SJ; School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, New South Wales, Australia.; Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Sydney, New South Wales, Australia.; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia., Menon U; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK., Rosenthal AN; Women's Cancer, Institute for Women's Health, University College London, London, UK., Jacobs I; Women's Cancer, Institute for Women's Health, University College London, London, UK.; University of New South Wales, Sydney, New South Wales, Australia.; University of Manchester, Manchester, UK., Gayther SA; Center for Bioinformatics and Functional Genomics and the Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Dicks E; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Nevanlinna H; Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland., Aittomäki K; Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland., Pelttari LM; Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland., Ehrencrona H; Department of Clinical Genetics and Pathology, Laboratory Medicine, Office for Medical Services, Region Skåne, Lund, Sweden.; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden., Borg Å; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden., Kvist A; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden., Rivera B; Gerald Bronfman Dept Oncology, Jewish General Hospital, McGill University and Lady Davis Institute, Montréal, QC, Canada.; Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, Hospitalet de Llobregat, Barcelona, Spain., Hansen TVO; Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Clinical Genetics Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Djursby M; Department of Clinical Genetics Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Lee A; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Dennis J; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Bowtell DD; Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.; Sir Peter MacCallum, Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Traficante N; Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.; Sir Peter MacCallum, Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Diez O; Oncogenetics Group, Vall dHebron Institute of Oncology, Barcelona, Spain.; Clinical and Molecular Genetics Area, University Hospital Vall dHebron, Barcelona, Spain., Balmaña J; Hereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.; Department of Medical Oncology, University Hospital of Vall d'Hebron, Barcelona, Spain., Gruber SB; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Chenevix-Trench G; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Investigators K; Kathleen Cuningham Foundation Consortium for research into Familial Breast cancer., Jensen A; Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark., Kjær SK; Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.; Department of Gynaecology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark., Høgdall E; Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.; Department of Pathology, Molecular Unit, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark., Castéra L; Department of Cancer Biology and Genetics, Normandy Centre for Genomic and Personalized Medicine, François Baclesse Center, Inserm U1245, Caen, France., Garber J; Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, MA, USA., Janavicius R; Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.; State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania., Osorio A; Centro de Investigación en Red de Enfermedades Raras, Madrid, Spain.; Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid, Spain., Golmard L; Institut Curie, Paris Sciences Lettres Research University, Service de Génétique, Paris, France., Vega A; Centro de Investigación en Red de Enfermedades Raras, Madrid, Spain.; Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.; Instituto de Investigación Sanitaria de Santiago de Compostela, Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain., Couch FJ; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Robson M; Department of Medicine, Memorial Sloan Kettering Cancer Center, Clinical Genetics Service, New York, NY, USA., Gronwald J; Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland., Domchek SM; Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA., Culver JO; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., de la Hoya M; Molecular Oncology Laboratory CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain., Easton DF; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Foulkes WD; Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, University of Cologne, Cologne, Germany.; Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany., Tischkowitz M; Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, University of Cologne, Cologne, Germany.; National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany., Meindl A; Department of Gynecology and Obstetrics, University of Munich, Campus Großhadern, Munich, Germany., Schmutzler RK; Faculty of Medicine and University Hospital Cologne, Center for Familial Breast and Ovarian Cancer, University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital Cologne, Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany., Pharoah PDP; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Antoniou AC; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
Jazyk:	angličtina
Zdroj:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2020 Dec 14; Vol. 112 (12), pp. 1242-1250.
DOI:	10.1093/jnci/djaa030
Abstrakt:	Background: The purpose of this study was to estimate precise age-specific tubo-ovarian carcinoma (TOC) and breast cancer (BC) risks for carriers of pathogenic variants in RAD51C and RAD51D. Methods: We analyzed data from 6178 families, 125 with pathogenic variants in RAD51C, and 6690 families, 60 with pathogenic variants in RAD51D. TOC and BC relative and cumulative risks were estimated using complex segregation analysis to model the cancer inheritance patterns in families while adjusting for the mode of ascertainment of each family. All statistical tests were two-sided. Results: Pathogenic variants in both RAD51C and RAD51D were associated with TOC (RAD51C: relative risk [RR] = 7.55, 95% confidence interval [CI] = 5.60 to 10.19; P = 5 × 10-40; RAD51D: RR = 7.60, 95% CI = 5.61 to 10.30; P = 5 × 10-39) and BC (RAD51C: RR = 1.99, 95% CI = 1.39 to 2.85; P = 1.55 × 10-4; RAD51D: RR = 1.83, 95% CI = 1.24 to 2.72; P = .002). For both RAD51C and RAD51D, there was a suggestion that the TOC relative risks increased with age until around age 60 years and decreased thereafter. The estimated cumulative risks of developing TOC to age 80 years were 11% (95% CI = 6% to 21%) for RAD51C and 13% (95% CI = 7% to 23%) for RAD51D pathogenic variant carriers. The estimated cumulative risks of developing BC to 80 years were 21% (95% CI = 15% to 29%) for RAD51C and 20% (95% CI = 14% to 28%) for RAD51D pathogenic variant carriers. Both TOC and BC risks for RAD51C and RAD51D pathogenic variant carriers varied by cancer family history and could be as high as 32-36% for TOC, for carriers with two first-degree relatives diagnosed with TOC, or 44-46% for BC, for carriers with two first-degree relatives diagnosed with BC. Conclusions: These estimates will facilitate the genetic counseling of RAD51C and RAD51D pathogenic variant carriers and justify the incorporation of RAD51C and RAD51D into cancer risk prediction models. (© The Author(s) 2020. Published by Oxford University Press.)
Databáze:	MEDLINE
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