학술논문

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers.
Document Type
Academic Journal
Author
Hakkaart C; Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.; Pearson JF; Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.; Marquart L; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; School of Public Health, University of Queensland, Brisbane, Australia.; Dennis J; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Wiggins GAR; Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.; Barnes DR; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Robinson BA; Department of Medicine, University of Otago, Christchurch, New Zealand.; Canterbury Regional Cancer and Haematology Service, Canterbury District Health Board, Christchurch Hospital, Christchurch, New Zealand.; Mace PD; Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.; Aittomäki K; Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland.; Andrulis IL; Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.; Arun BK; Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Azzollini J; Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.; Balmaña J; Hereditary cancer Genetics Group, Vall d'Hebron Institute of Oncology, Vall d'Hebron Hospital Campus, Barcelona, Spain.; Department of Medical Oncology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.; Barkardottir RB; Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.; BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik, Iceland.; Belhadj S; Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Berger L; Department of Clinical Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Blok MJ; Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.; Boonen SE; Department of Clinical Genetics, Odense University Hospital, Odence C, Denmark.; Borde J; 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.; Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Bradbury AR; Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Brunet J; Hereditary Cancer Program, Catalan Institute of Oncology (ICO), ONCOBELL-IDIBELL-IGTP, CIBERONC, Barcelona, Spain.; Buys SS; Department of Medicine, Huntsman Cancer Institute, Salt Lake City, UT, USA.; Caligo MA; SOD Genetica Molecolare, University Hospital, Pisa, Italy.; Campbell I; Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.; Chung WK; Departments of Pediatrics and Medicine, Columbia University, New York, NY, USA.; Claes KBM; Centre for Medical Genetics, Ghent University Hospital, Gent, Belgium.; Collonge-Rame MA; Service de Génétique Biologique, CHRU de Besançon, Besançon, France.; Cook J; Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK.; Cosgrove C; Gynecologic Oncology, Translational Therapeutics, Department of Obstetrics and Gynecology, Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Couch FJ; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.; Daly MB; Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.; Dandiker S; Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Davidson R; Department of Clinical Genetics, Queen Elizabeth University Hospital, Glasgow, UK.; de la Hoya M; Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain.; de Putter R; Centre for Medical Genetics, Ghent University Hospital, Gent, Belgium.; Delnatte C; Oncogénétique, Institut de Cancérologie de l'Ouest siteRené Gauducheau, Saint Herblain, France.; Dhawan M; Cancer Genetics and Prevention Program, University of California San Francisco, San Francisco, CA, USA.; Diez O; Hereditary cancer Genetics Group, Vall d'Hebron Institute of Oncology, Vall d'Hebron Hospital Campus, Barcelona, Spain.; Area of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.; Ding YC; Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.; Domchek SM; Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.; Donaldson A; Clinical Genetics Department, St Michael's Hospital, Bristol, UK.; Eason J; Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, 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.; Ehrencrona H; Department of Clinical Genetics and Pathology, Laboratory Medicine, Skåne University Hospital, Lund, Sweden.; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.; 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.; Faust U; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.; Feliubadaló L; Hereditary Cancer Program, Catalan Institute of Oncology (ICO), ONCOBELL-IDIBELL-IGTP, CIBERONC, Barcelona, Spain.; Fostira F; Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens, Greece.; Friedman E; The Susanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, Ramat Gan, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.; Frone M; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.; Frost D; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Garber J; Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, MA, USA.; Gayther SA; Center for Bioinformatics and Functional Genomics and the Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Gehrig A; Department of Human Genetics, University Würzburg, Würzburg, Germany.; Gesta P; Service Régional Oncogénétique Poitou-Charentes, CH Niort, Niort, France.; Godwin AK; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.; Goldgar DE; Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.; Greene MH; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.; Hahnen E; Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Hake CR; Waukesha Memorial Hospital-Pro Health Care, Waukesha, USA.; Hamann U; Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Hansen TVO; Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; Hauke J; 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.; Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Hentschel J; Institute of Human Genetics, University Hospital Leipzig, Leipzig, Germany.; Herold N; 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.; Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Honisch E; Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.; Hulick PJ; Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL, USA.; The University of Chicago Pritzker School of Medicine, Chicago, IL, USA.; Imyanitov EN; N.N. Petrov Institute of Oncology, St. Petersburg, Russia.; Isaacs C; Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.; Izatt L; Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.; Izquierdo A; Hereditary Cancer Program, Catalan Institute of Oncology (ICO), ONCOBELL-IDIBELL-IGTP, CIBERONC, Barcelona, Spain.; Jakubowska A; Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.; Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland.; James PA; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.; Parkville Familial Cancer Centre, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.; Janavicius R; Faculty of Medicine, Institute of Biomedical Sciences, Dept. Of Human and Medical Genetics, Vilnius University, Vilnius, Lithuania.; State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.; John EM; Department of Epidemiology & Population Health, Stanford University School of Medicine, Stanford, CA, USA.; Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.; Joseph V; Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Karlan BY; David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, CA, USA.; Kemp Z; Breast and Cancer Genetics Units, The Royal Marsden NHS Foundation Trust, London, UK.; Kirk J; Familial Cancer Service, Weatmead Hospital, Wentworthville, New South Wales, Australia.; Konstantopoulou I; Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens, Greece.; Koudijs M; Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands.; Kwong A; Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong, China.; Department of Surgery, The University of Hong Kong, Hong Kong, China.; Department of Surgery and Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong, China.; Laitman Y; The Susanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, Ramat Gan, Israel.; Lalloo F; Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA.; Lasset C; Unité de Prévention et d'Epidémiologie Génétique, Centre Léon Bérard, Lyon, France.; Lautrup C; Department of Clinical Genetics, Aarhus University Hospital, Aarhus N, Denmark.; Lazaro C; Hereditary Cancer Program, Catalan Institute of Oncology (ICO), ONCOBELL-IDIBELL-IGTP, CIBERONC, Barcelona, Spain.; Legrand C; Département de Génétique, CHU de Grenoble, Grenoble, France.; Leslie G; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Lesueur F; Genetic Epidemiology of Cancer team, Inserm U900, Paris, France.; Institut Curie, Paris, France.; Mines ParisTech, Fontainebleau, France.; Mai PL; Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Manoukian S; Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.; Mari V; Département d'Hématologie-Oncologie Médicale, Centre Antoine Lacassagne, Nice, France.; Martens JWM; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.; McGuffog L; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Mebirouk N; Genetic Epidemiology of Cancer team, Inserm U900, Paris, France.; Institut Curie, Paris, France.; Mines ParisTech, Fontainebleau, France.; Meindl A; Department of Gynecology and Obstetrics, University of Munich, Campus Großhadern, Munich, Germany.; Miller A; NRG Oncology, Statistics and Data Management Center, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.; Montagna M; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.; Moserle L; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.; Mouret-Fourme E; Service de Génétique, Institut Curie, Paris, France.; Musgrave H; Department of Clinical Genetics, Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK.; Nambot S; Unité d'oncogénétique, Centre de Lutte Contre le Cancer, Centre Georges-François Leclerc, Dijon, France.; Nathanson KL; Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.; Neuhausen SL; Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.; Nevanlinna H; Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.; Yie JNY; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.; Cancer Genetics Service, National Cancer Centre, Singapore, Singapore.; Nguyen-Dumont T; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.; Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia.; Nikitina-Zake L; Latvian Biomedical Research and Study Centre, Riga, Latvia.; Offit K; Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Olah E; Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.; Olopade OI; Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL, USA.; Osorio A; Familial Cancer Clinical Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO) and Spanish Network on Rare Diseases (CIBERER), Madrid, Spain.; Ott CE; Institute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Park SK; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.; Integrated Major in Innovative Medical Science, Seoul National University College of Medicine, Seoul, South Korea.; Cancer Research Institute, Seoul National University, Seoul, Korea.; Parsons MT; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; Pedersen IS; Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark.; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.; Peixoto A; Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.; Perez-Segura P; Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain.; Peterlongo P; Genome Diagnostics Program, IFOM ETS - the AIRC Institute of Molecular Oncology, Milan, Italy.; Pocza T; Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.; Radice P; Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.; Ramser J; Division of Gynaecology and Obstetrics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.; Rantala J; Clinical Genetics, Karolinska Institutet, Stockholm, Sweden.; Rodriguez GC; Division of Gynecologic Oncology, NorthShore University HealthSystem, University of Chicago, Evanston, IL, USA.; Rønlund K; Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle Hospital, Vejle, Denmark.; Rosenberg EH; Department of Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.; Rossing M; Center for Genomic Medicine, Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Schmutzler RK; 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.; Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Shah PD; Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Sharif S; West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Birmingham, UK.; Sharma P; Department of Internal Medicine, Division of Medical Oncology, University of Kansas Medical Center, Westwood, KS, USA.; Side LE; Princess Anne Hospital, Southampton, UK.; Simard J; Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval Research Center, Québec City, QC, Canada.; Singer CF; Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.; Snape K; Medical Genetics Unit, St George's, University of London, London, UK.; Steinemann D; Institute of Human Genetics, Hannover Medical School, Hannover, Germany.; Stoppa-Lyonnet D; Service de Génétique, Institut Curie, Paris, France.; Department of Tumour Biology, INSERM U830, Paris, France.; Université Paris Cité, Paris, France.; Sutter C; Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany.; Tan YY; Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.; Teixeira MR; Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.; Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.; Teo SH; Breast Cancer Research Programme, Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.; Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.; Thomassen M; Department of Clinical Genetics, Odense University Hospital, Odence C, Denmark.; Thull DL; Department of Medicine, Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Tischkowitz M; Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montréal, QC, Canada.; Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.; Toland AE; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.; Trainer AH; Parkville Familial Cancer Centre, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.; Department of medicine, University Of Melbourne, Melbourne, Victoria, Australia.; Tripathi V; South East Thames Regional Genetics Service, Guy's and St Thomas' NHS Foundation Trust, London, UK.; Tung N; Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.; van Engelen K; Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.; van Rensburg EJ; Department of Genetics, University of Pretoria, Arcadia, South Africa.; 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.; Viel A; Division of Functional onco-genomics and genetics, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.; Walker L; Oxford Regional Genetics Service, Churchill Hospital, Oxford, UK.; Weitzel JN; Latin American School of Oncology, Tuxtla Gutiérrez, Chiapas, Mexico.; Wevers MR; Radboud University Medical Center, Nijmegen, Netherlands.; Chenevix-Trench G; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; Spurdle AB; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; Antoniou AC; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Walker LC; Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand. logan.walker@otago.ac.nz.
Source
Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE
Subject
Language
English
Abstract
The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
(© 2022. The Author(s).)