Leila Dorling1, Sara Carvalho1, Jamie Allen1, Anna González-Neira1, Craig Luccarini1, Cecilia Wahlström1, Karen A Pooley1, Michael T Parsons1, Cristina Fortuno1, Qin Wang1, Manjeet K Bolla1, Joe Dennis1, Renske Keeman1, M Rosario Alonso1, Nuria Álvarez1, Belen Herraez1, Victoria Fernandez1, Rocio Núñez-Torres1, Ana Osorio1, Jeanette Valcich1, Minerva Li1, Therese Törngren1, Patricia A Harrington1, Caroline Baynes1, Don M Conroy1, Brennan Decker1, Laura Fachal1, Nasim Mavaddat1, Thomas Ahearn1, Kristiina Aittomäki1, Natalia N Antonenkova1, Norbert Arnold1, Patrick Arveux1, Margreet G E M Ausems1, Päivi Auvinen1, Heiko Becher1, Matthias W Beckmann1, Sabine Behrens1, Marina Bermisheva1, Katarzyna Białkowska1, Carl Blomqvist1, Natalia V Bogdanova1, Nadja Bogdanova-Markov1, Stig E Bojesen1, Bernardo Bonanni1, Anne-Lise Børresen-Dale1, Hiltrud Brauch1, Michael Bremer1, Ignacio Briceno1, Thomas Brüning1, Barbara Burwinkel1, David A Cameron1, Nicola J Camp1, Archie Campbell1, Angel Carracedo1, Jose E Castelao1, Melissa H Cessna1, Stephen J Chanock1, Hans Christiansen1, J Margriet Collée1, Emilie Cordina-Duverger1, Sten Cornelissen1, Kamila Czene1, Thilo Dörk1, Arif B Ekici1, Christoph Engel1, Mikael Eriksson1, Peter A Fasching1, Jonine Figueroa1, Henrik Flyger1, Asta Försti1, Marike Gabrielson1, Manuela Gago-Dominguez1, Vassilios Georgoulias1, Fabian Gil1, Graham G Giles1, Gord Glendon1, Encarna B Gómez Garcia1, Grethe I Grenaker Alnæs1, Pascal Guénel1, Andreas Hadjisavvas1, Lothar Haeberle1, Eric Hahnen1, Per Hall1, Ute Hamann1, Elaine F Harkness1, Jaana M Hartikainen1, Mikael Hartman1, Wei He1, Bernadette A M Heemskerk-Gerritsen1, Peter Hillemanns1, Frans B L Hogervorst1, Antoinette Hollestelle1, Weang Kee Ho1, Maartje J Hooning1, Anthony Howell1, Keith Humphreys1, Faiza Idris1, Anna Jakubowska1, Audrey Jung1, Pooja Middha Kapoor1, Michael J Kerin1, Elza Khusnutdinova1, Sung-Won Kim1, Yon-Dschun Ko1, Veli-Matti Kosma1, Vessela N Kristensen1, Kyriacos Kyriacou1, Inge M M Lakeman1, Jong Won Lee1, Min Hyuk Lee1, Jingmei Li1, Annika Lindblom1, Wing-Yee Lo1, Maria A Loizidou1, Artitaya Lophatananon1, Jan Lubiński1, Robert J MacInnis1, Michael J Madsen1, Arto Mannermaa1, Mehdi Manoochehri1, Siranoush Manoukian1, Sara Margolin1, Maria Elena Martinez1, Tabea Maurer1, Dimitrios Mavroudis1, Catriona McLean1, Alfons Meindl1, Arjen R Mensenkamp1, Kyriaki Michailidou1, Nicola Miller1, Nur Aishah Mohd Taib1, Kenneth Muir1, Anna Marie Mulligan1, Heli Nevanlinna1, William G Newman1, Børge G Nordestgaard1, Pei-Sze Ng1, Jan C Oosterwijk1, Sue K Park1, Tjoung-Won Park-Simon1, Jose I A Perez1, Paolo Peterlongo1, David J Porteous1, Karolina Prajzendanc1, Darya Prokofyeva1, Paolo Radice1, Muhammad U Rashid1, Valerie Rhenius1, Matti A Rookus1, Thomas Rüdiger1, Emmanouil Saloustros1, Elinor J Sawyer1, Rita K Schmutzler1, Andreas Schneeweiss1, Peter Schürmann1, Mitul Shah1, Christof Sohn1, Melissa C Southey1, Harald Surowy1, Maija Suvanto1, Somchai Thanasitthichai1, Ian Tomlinson1, Diana Torres1, Thérèse Truong1, Maria Tzardi1, Yana Valova1, Christi J van Asperen1, Rob M Van Dam1, Ans M W van den Ouweland1, Lizet E van der Kolk1, Elke M van Veen1, Camilla Wendt1, Justin A Williams1, Xiaohong R Yang1, Sook-Yee Yoon1, M Pilar Zamora1, D Gareth Evans1, Miguel de la Hoya1, Jacques Simard1, Antonis C Antoniou1, Åke Borg1, Irene L Andrulis1, Jenny Chang-Claude1, Montserrat García-Closas1, Georgia Chenevix-Trench1, Roger L Milne1, Paul D P Pharoah1, Marjanka K Schmidt1, Amanda B Spurdle1, Maaike P G Vreeswijk1, Javier Benitez1, Alison M Dunning1, Anders Kvist1, Soo H Teo1, Peter Devilee1, Douglas F Easton1. 1. The authors' affiliations are as follows: the Centre for Cancer Genetic Epidemiology, Departments of Public Health and Primary Care (L.D., S. Carvalho, J.A., K.A.P., Q.W., M.K.B., J.D., B.D., N. Mavaddat, K. Michailidou, A.C.A., P.D.P.P., D.F.E.) and Oncology (C.L., P.A.H., C. Baynes, D.M.C., L.F., V.R., M. Shah, P.D.P.P., A.M.D., D.F.E.), University of Cambridge, Cambridge, the Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine (A. Campbell, D.J.P.), and the Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology (D.J.P.), University of Edinburgh, the Cancer Research UK Edinburgh Centre (D.A.C., J.F.), and the Usher Institute of Population Health Sciences and Informatics, University of Edinburgh Medical School (A. Campbell, J.F.), Edinburgh, the Divisions of Informatics, Imaging, and Data Sciences (E.F.H.), Cancer Sciences (A. Howell), Population Health, Health Services Research, and Primary Care (A. Lophatananon, K. Muir), and Evolution and Genomic Sciences, School of Biological Sciences (W.G.N., E.M.V., D.G.E.), University of Manchester, the NIHR Manchester Biomedical Research Unit (E.F.H.) and the Nightingale Breast Screening Centre, Wythenshawe Hospital (E.F.H., H.I.), Academic Health Science Centre and North West Genomics Laboratory Hub, and the Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester University NHS Foundation Trust (W.G.N., E.M.V., D.G.E.), Manchester, the School of Cancer and Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, King's College London, London (E.J.S.), the Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham (I.T.), and the Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford (I.T.) - all in the United Kingdom; the Human Genotyping-CEGEN Unit, Human Cancer Genetic Program (A.G.-N., M.R.A., N.Á., B.H., R.N.-T.), and the Human Genetics Group (V.F., A.O., J.B.), Spanish National Cancer Research Center, Centro de Investigación en Red de Enfermedades Raras (A.O., J.B.), Servicio de Oncología Médica, Hospital Universitario La Paz (M.P.Z.), and Molecular Oncology Laboratory, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (M. de la Hoya), Madrid, the Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela, Complejo Hospitalario Universitario de Santiago (A. Carracedo, M.G.-D.), and Centro de Investigación en Red de Enfermedades Raras y Centro Nacional de Genotipado, Universidad de Santiago de Compostela (A. Carracedo), Santiago de Compostela, the Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur, Xerencia de Xestion Integrada de Vigo-Servizo Galeo de Saúde, Vigo (J.E.C.), and Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo (J.I.A.P.) - all in Spain; the Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund (C. Wahlström, J.V., M.L., T. Törngren, Å.B., A.K.), the Department of Oncology, Örebro University Hospital, Örebro (C. Blomqvist), and the Departments of Medical Epidemiology and Biostatistics (K.C., M.E., M.G., P. Hall, W.H., K.H.), Oncology, Södersjukhuset (P. Hall, S. Margolin), Molecular Medicine and Surgery (A. Lindblom), and Clinical Science and Education, Södersjukhuset (S. Margolin, C. Wendt), Karolinska Institutet, and the Department of Clinical Genetics, Karolinska University Hospital (A. Lindblom), Stockholm - all in Sweden; the Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD (M.T.P., C.F., G.C.-T., A.B.S.), the Cancer Epidemiology Division, Cancer Council Victoria (G.G.G., R.J.M., R.L.M.), the Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health (G.G.G., R.J.M., R.L.M.), and the Department of Clinical Pathology (M.C.S.), University of Melbourne, Anatomical Pathology, Alfred Hospital (C.M.), and the Cancer Epidemiology Division, Cancer Council Victoria (M.C.S.), Melbourne, VIC, and Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC (G.G.G., M.C.S., R.L.M.) - all in Australia; the Division of Molecular Pathology (R.K., S. Cornelissen, M.K.S.), Family Cancer Clinic (F.B.L.H., L.E.K.), Department of Epidemiology (M.A.R.), and Division of Psychosocial Research and Epidemiology (M.K.S.), the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, Division Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Center, Utrecht (M.G.E.M.A.), the Department of Clinical Genetics, Erasmus University Medical Center (J.M.C., A.M.W.O.), and the Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute (B.A.M.H.-G., A. Hollestelle, M.J.H.), Rotterdam, the Department of Clinical Genetics, Maastricht University Medical Center, Maastricht (E.B.G.G.), the Departments of Human Genetics (I.M.M.L., M.P.G.V., P.D.), Clinical Genetics (C.J.A.), and Pathology (P.D.), Leiden University Medical Center, Leiden, the Department of Human Genetics, Radboud University Medical Center, Nijmegen (A.R.M.), and the Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen (J.C.O.) - all in the Netherlands; the Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute (B.D.), and the Division of Cancer Epidemiology and Genetics, National Cancer Institute (T.A., S.J.C., X.R.Y., M.G.-C.), National Institutes of Health, Bethesda, MD; the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School (B.D.), and the Department of Nutrition, Harvard T.H. Chan School of Public Health (R.M.V.D.), Boston; the Departments of Clinical Genetics (K.A.), Oncology (C. Blomqvist), and Obstetrics and Gynecology (H.N., M. Suvanto), Helsinki University Hospital, University of Helsinki, Helsinki, and the Unit of Clinical Oncology, Kuopio University Hospital (P. Auvinen), the Institute of Clinical Medicine, Oncology (P. Auvinen), the Translational Cancer Research Area (J.M.H., V.-M.K., A. Mannermaa), and the Institute of Clinical Medicine, Pathology, and Forensic Medicine (J.M.H., V.-M.K., A. Mannermaa), University of Eastern Finland, and the Biobank of Eastern Finland, Kuopio University Hospital (V.-M.K., A. Mannermaa), Kuopio - both in Finland; the N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus (N.N.A., N.V.B.); the Department of Gynecology and Obstetrics and Institute of Clinical Molecular Biology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel (N.A.), the Institute of Medical Biometry and Epidemiology (H. Becher) and Cancer Epidemiology Group (T.M., J.C.-C.), University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, the Department of Gynecology and Obstetrics (M.W.B., P.A.F., L.H.) and Institute of Human Genetics (A.B.E.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, Erlangen, the Division of Cancer Epidemiology (S.B., A. Jung, P.M.K., J.C.-C.), Molecular Epidemiology Group, C080 (B. Burwinkel, H.S.), Division of Pediatric Neurooncology (A.F.), and Molecular Genetics of Breast Cancer (U.H., M.M., M.U.R., D.T.), German Cancer Research Center, Molecular Biology of Breast Cancer, University Women's Clinic Heidelberg, University of Heidelberg (B. Burwinkel, A.S., H.S.), Hopp Children's Cancer Center (A.F.), Faculty of Medicine, University of Heidelberg (P.M.K.), and National Center for Tumor Diseases, University Hospital and German Cancer Research Center (A.S., C.S.), Heidelberg, the Department of Radiation Oncology (N.V.B., M. Bremer, H.C.) and the Gynecology Research Unit (N.V.B., T.D., P. Hillemanns, T.-W.P.-S., P.S.), Hannover Medical School, Hannover, the Institute of Human Genetics, University of Münster, Münster (N.B.-M.), Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart (H. Brauch, W.-Y.L.), iFIT-Cluster of Excellence, University of Tübingen, and the German Cancer Consortium, German Cancer Research Center, Partner Site Tübingen (H. Brauch), and the University of Tübingen (W.-Y.L.), Tübingen, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, Bochum (T.B.), Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig (C.E.), Center for Hereditary Breast and Ovarian Cancer (E.H., R.K.S.) and Center for Integrated Oncology (E.H., R.K.S.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, the Department of Internal Medicine, Evangelische Kliniken Bonn, Johanniter Krankenhaus, Bonn (Y.-D.K.), the Department of Gynecology and Obstetrics, University of Munich, Campus Großhadern, Munich (A. Meindl), and the Institute of Pathology, Städtisches Klinikum Karlsruhe, Karlsruhe (T.R.) - all in Germany; the Gynecological Cancer Registry, Centre Georges-François Leclerc, Dijon (P. Arveux), and the Center for Research in Epidemiology and Population Health, Team Exposome and Heredity, INSERM, University Paris-Saclay, Villejuif (E.C.-D., P.G., T. Truong) - both in France; the Institute of Biochemistry and Genetics, Ufa Federal Research Center of the Russian Academy of Sciences (M. Bermisheva, E.K.), the Department of Genetics and Fundamental Medicine, Bashkir State University (E.K., D.P., Y.V.), and the Ufa Research Institute of Occupational Health and Human Ecology (Y.V.), Ufa, Russia; the Department of Genetics and Pathology (K.B., A. Jakubowska, J. Lubiński, K.P.) and the Independent Laboratory of Molecular Biology and Genetic Diagnostics (A. Jakubowska), Pomeranian Medical University, Szczecin, Poland; the Copenhagen General Population Study, the Department of Clinical Biochemistry (S.E.B., B.G.N.), and the Department of Breast Surgery (H.F.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, and the Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (S.E.B., B.G.N.) - both in Denmark; the Division of Cancer Prevention and Genetics, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) (B. Bonanni), the Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (S. Manoukian), the Genome Diagnostics Program, FIRC Institute of Molecular Oncology (P.P.), and the Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (P.R.), Milan; the Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet (A.-L.B.-D., G.I.G.A., V.N.K.), and the Institute of Clinical Medicine, Faculty of Medicine, University of Oslo (A.-L.B.-D., V.N.K.), Oslo; Medical Faculty, Universidad de La Sabana (I.B.), and the Clinical Epidemiology and Biostatistics Department (F.G.) and Institute of Human Genetics (D.T.), Pontificia Universidad Javeriana, Bogota, Colombia; the Department of Internal Medicine and Huntsman Cancer Institute, University of Utah (N.J.C., M.J.M., J.A.W.), and the Intermountain Healthcare Biorepository and Department of Pathology, Intermountain Healthcare (M.H.C.), Salt Lake City; the David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California, Los Angeles (P.A.F.), and Moores Cancer Center (M.G.-D., M.E.M.) and the Department of Family Medicine and Public Health (M.E.M.), University of California San Diego, La Jolla; the Departments of Medical Oncology (V.G., D.M.) and Pathology (M.T.), University Hospital of Heraklion, Heraklion, and the Department of Oncology, University Hospital of Larissa, Larissa (E.S.) - both in Greece; the Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital (G.G., I.L.A.), the Departments of Laboratory Medicine and Pathobiology (A.M.M.) and Molecular Genetics (I.L.A.), University of Toronto, and the Laboratory Medicine Program, University Health Network (A.M.M.), Toronto, and the Genomics Center, Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Québec City, QC (J.S.) - both in Canada; the Department of Electron Microscopy and Molecular Pathology (A. Hadjisavvas, K.K., M.A.L.), the Cyprus School of Molecular Medicine (A. Hadjisavvas, K.K., M.A.L., K. Michailidou), and the Biostatistics Unit (K. Michailidou), Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; the Saw Swee Hock School of Public Health (M. Hartman, R.M.V.D.) and the Department of Medicine, Yong Loo Lin School of Medicine (R.M.V.D.), National University of Singapore, the Department of Surgery, National University Health System (M. Hartman, J. Li), and the Human Genetics Division, Genome Institute of Singapore (J. Li), Singapore; the Department of Mathematical Sciences, Faculty of Science and Engineering, University of Nottingham Malaysia (W.K.H.), and the Breast Cancer Research Programme, Cancer Research Malaysia (W.K.H., P.S.N., S.-Y.Y., S.H.T.), Selangor, and the Breast Cancer Research Unit, Cancer Research Institute (N.A.M.T.), and the Department of Surgery, Faculty of Medicine (N.A.M.T., P.S.N., S.H.T.), University Malaya, Kuala Lumpur - both in Malaysia; Surgery, School of Medicine, National University of Ireland, Galway (M.J.K., N. Miller); the Department of Surgery, Daerim Saint Mary's Hospital (S.-W.K.), the Department of Surgery, Ulsan University College of Medicine and Asan Medical Center (J.W.L.), the Department of Surgery, Soonchunhyang University College of Medicine and Soonchunhyang University Hospital (M.H.L.), Integrated Major in Innovative Medical Science, Seoul National University College of Medicine (S.K.P.), and the Cancer Research Institute, Seoul National University (S.K.P.), Seoul, South Korea; the Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan (M.U.R.); and the National Cancer Institute, Ministry of Public Health, Nonthaburi, Thailand (S.T.).
Abstract
BACKGROUND: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking. METHODS: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity. RESULTS: Protein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants. CONCLUSIONS: The results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.).
BACKGROUND: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking. METHODS: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity. RESULTS: Protein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants. CONCLUSIONS: The results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.).
Authors: Sean V Tavtigian; Peter J Oefner; Davit Babikyan; Anne Hartmann; Sue Healey; Florence Le Calvez-Kelm; Fabienne Lesueur; Graham B Byrnes; Shu-Chun Chuang; Nathalie Forey; Corinna Feuchtinger; Lydie Gioia; Janet Hall; Mia Hashibe; Barbara Herte; Sandrine McKay-Chopin; Alun Thomas; Maxime P Vallée; Catherine Voegele; Penelope M Webb; David C Whiteman; Suleeporn Sangrajrang; John L Hopper; Melissa C Southey; Irene L Andrulis; Esther M John; Georgia Chenevix-Trench Journal: Am J Hum Genet Date: 2009-09-24 Impact factor: 11.025
Authors: Caroline J Watson; A L Papula; Gladys Y P Poon; Wing H Wong; Andrew L Young; Todd E Druley; Daniel S Fisher; Jamie R Blundell Journal: Science Date: 2020-03-27 Impact factor: 47.728
Authors: Douglas F Easton; Paul D P Pharoah; Antonis C Antoniou; Marc Tischkowitz; Sean V Tavtigian; Katherine L Nathanson; Peter Devilee; Alfons Meindl; Fergus J Couch; Melissa Southey; David E Goldgar; D Gareth R Evans; Georgia Chenevix-Trench; Nazneen Rahman; Mark Robson; Susan M Domchek; William D Foulkes Journal: N Engl J Med Date: 2015-05-27 Impact factor: 91.245
Authors: Amanda B Spurdle; Stephanie Greville-Heygate; Antonis C Antoniou; Melissa Brown; Leslie Burke; Miguel de la Hoya; Susan Domchek; Thilo Dörk; Helen V Firth; Alvaro N Monteiro; Arjen Mensenkamp; Michael T Parsons; Paolo Radice; Mark Robson; Marc Tischkowitz; Emma Tudini; Clare Turnbull; Maaike Pg Vreeswijk; Logan C Walker; Sean Tavtigian; Diana M Eccles Journal: J Med Genet Date: 2019-04-08 Impact factor: 5.941
Authors: Karoline B Kuchenbaecker; John L Hopper; Daniel R Barnes; Kelly-Anne Phillips; Thea M Mooij; Marie-José Roos-Blom; Sarah Jervis; Flora E van Leeuwen; Roger L Milne; Nadine Andrieu; David E Goldgar; Mary Beth Terry; Matti A Rookus; Douglas F Easton; Antonis C Antoniou; Lesley McGuffog; D Gareth Evans; Daniel Barrowdale; Debra Frost; Julian Adlard; Kai-Ren Ong; Louise Izatt; Marc Tischkowitz; Ros Eeles; Rosemarie Davidson; Shirley Hodgson; Steve Ellis; Catherine Nogues; Christine Lasset; Dominique Stoppa-Lyonnet; Jean-Pierre Fricker; Laurence Faivre; Pascaline Berthet; Maartje J Hooning; Lizet E van der Kolk; Carolien M Kets; Muriel A Adank; Esther M John; Wendy K Chung; Irene L Andrulis; Melissa Southey; Mary B Daly; Saundra S Buys; Ana Osorio; Christoph Engel; Karin Kast; Rita K Schmutzler; Trinidad Caldes; Anna Jakubowska; Jacques Simard; Michael L Friedlander; Sue-Anne McLachlan; Eva Machackova; Lenka Foretova; Yen Y Tan; Christian F Singer; Edith Olah; Anne-Marie Gerdes; Brita Arver; Håkan Olsson Journal: JAMA Date: 2017-06-20 Impact factor: 56.272
Authors: Andrew Lee; Nasim Mavaddat; Amber N Wilcox; Alex P Cunningham; Tim Carver; Simon Hartley; Chantal Babb de Villiers; Angel Izquierdo; Jacques Simard; Marjanka K Schmidt; Fiona M Walter; Nilanjan Chatterjee; Montserrat Garcia-Closas; Marc Tischkowitz; Paul Pharoah; Douglas F Easton; Antonis C Antoniou Journal: Genet Med Date: 2019-01-15 Impact factor: 8.822
Authors: Allison W Kurian; Paul Abrahamse; Kevin C Ward; Ann S Hamilton; Dennis Deapen; Jonathan S Berek; Lily Hoang; Amal Yussuf; Jill Dolinsky; Krystal Brown; Thomas Slavin; Timothy P Hofer; Steven J Katz Journal: JCO Precis Oncol Date: 2021-12-22
Authors: Joe Dennis; Jonathan P Tyrer; Logan C Walker; Kyriaki Michailidou; Leila Dorling; Manjeet K Bolla; Qin Wang; Thomas U Ahearn; Irene L Andrulis; Hoda Anton-Culver; Natalia N Antonenkova; Volker Arndt; Kristan J Aronson; Laura E Beane Freeman; Matthias W Beckmann; Sabine Behrens; Javier Benitez; Marina Bermisheva; Natalia V Bogdanova; Stig E Bojesen; Hermann Brenner; Jose E Castelao; Jenny Chang-Claude; Georgia Chenevix-Trench; Christine L Clarke; J Margriet Collée; Fergus J Couch; Angela Cox; Simon S Cross; Kamila Czene; Peter Devilee; Thilo Dörk; Laure Dossus; A Heather Eliassen; Mikael Eriksson; D Gareth Evans; Peter A Fasching; Jonine Figueroa; Olivia Fletcher; Henrik Flyger; Lin Fritschi; Marike Gabrielson; Manuela Gago-Dominguez; Montserrat García-Closas; Graham G Giles; Anna González-Neira; Pascal Guénel; Eric Hahnen; Christopher A Haiman; Per Hall; Antoinette Hollestelle; Reiner Hoppe; John L Hopper; Anthony Howell; Agnes Jager; Anna Jakubowska; Esther M John; Nichola Johnson; Michael E Jones; Audrey Jung; Rudolf Kaaks; Renske Keeman; Elza Khusnutdinova; Cari M Kitahara; Yon-Dschun Ko; Veli-Matti Kosma; Stella Koutros; Peter Kraft; Vessela N Kristensen; Katerina Kubelka-Sabit; Allison W Kurian; James V Lacey; Diether Lambrechts; Nicole L Larson; Martha Linet; Alicja Ogrodniczak; Arto Mannermaa; Siranoush Manoukian; Sara Margolin; Dimitrios Mavroudis; Roger L Milne; Taru A Muranen; Rachel A Murphy; Heli Nevanlinna; Janet E Olson; Håkan Olsson; Tjoung-Won Park-Simon; Charles M Perou; Paolo Peterlongo; Dijana Plaseska-Karanfilska; Katri Pylkäs; Gad Rennert; Emmanouil Saloustros; Dale P Sandler; Elinor J Sawyer; Marjanka K Schmidt; Rita K Schmutzler; Rana Shibli; Ann Smeets; Penny Soucy; Melissa C Southey; Anthony J Swerdlow; Rulla M Tamimi; Jack A Taylor; Lauren R Teras; Mary Beth Terry; Ian Tomlinson; Melissa A Troester; Thérèse Truong; Celine M Vachon; Camilla Wendt; Robert Winqvist; Alicja Wolk; Xiaohong R Yang; Wei Zheng; Argyrios Ziogas; Jacques Simard; Alison M Dunning; Paul D P Pharoah; Douglas F Easton Journal: Commun Biol Date: 2022-01-18
Authors: Andrew N J Tutt; Judy E Garber; Bella Kaufman; Giuseppe Viale; Debora Fumagalli; Priya Rastogi; Richard D Gelber; Evandro de Azambuja; Anitra Fielding; Judith Balmaña; Susan M Domchek; Karen A Gelmon; Simon J Hollingsworth; Larissa A Korde; Barbro Linderholm; Hanna Bandos; Elżbieta Senkus; Jennifer M Suga; Zhimin Shao; Andrew W Pippas; Zbigniew Nowecki; Tomasz Huzarski; Patricia A Ganz; Peter C Lucas; Nigel Baker; Sibylle Loibl; Robin McConnell; Martine Piccart; Rita Schmutzler; Guenther G Steger; Joseph P Costantino; Amal Arahmani; Norman Wolmark; Eleanor McFadden; Vassiliki Karantza; Sunil R Lakhani; Greg Yothers; Christine Campbell; Charles E Geyer Journal: N Engl J Med Date: 2021-06-03 Impact factor: 176.079