Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

Helian Feng^{1

2

3}, Alexander Gusev⁴, Bogdan Pasaniuc⁵, Lang Wu⁶, Jirong Long⁷, Zomoroda Abu-Full⁸, Kristiina Aittomäki⁹, Irene L Andrulis^{10

11}, Hoda Anton-Culver¹², Antonis C Antoniou¹³, Adalgeir Arason^{14

15}, Volker Arndt¹⁶, Kristan J Aronson¹⁷, Banu K Arun¹⁸, Ella Asseryanis¹⁹, Paul L Auer^{20

21}, Jacopo Azzollini²², Judith Balmaña²³, Rosa B Barkardottir^{14

15}, Daniel R Barnes¹³, Daniel Barrowdale¹³, Matthias W Beckmann²⁴, Sabine Behrens²⁵, Javier Benitez^{26

27}, Marina Bermisheva²⁸, Katarzyna Białkowska²⁹, Ana Blanco^{26

30

31}, Carl Blomqvist^{32

33}, Bram Boeckx^{34

35}, Natalia V Bogdanova^{36

37

38}, Stig E Bojesen^{39

40

41}, Manjeet K Bolla¹³, Bernardo Bonanni⁴², Ake Borg⁴³, Hiltrud Brauch^{44

45

46}, Hermann Brenner^{16

46

47}, Ignacio Briceno^{48

49}, Annegien Broeks⁵⁰, Thomas Brüning⁵¹, Barbara Burwinkel^{52

53}, Qiuyin Cai⁷, Trinidad Caldés⁵⁴, Maria A Caligo⁵⁵, Ian Campbell^{56

57}, Sander Canisius^{50

58}, Daniele Campa⁵⁹, Brian D Carter⁶⁰, Jonathan Carter⁶¹, Jose E Castelao⁶², Jenny Chang-Claude^{25

63}, Stephen J Chanock⁶⁴, Hans Christiansen³⁶, Wendy K Chung⁶⁵, Kathleen B M Claes⁶⁶, Christine L Clarke⁶⁷; GEMO Study Collaborators^{68

69

70}; EMBRACE Collaborators¹³; GC-HBOC study Collaborators⁷¹; Fergus J Couch⁷², Angela Cox⁷³, Simon S Cross⁷⁴, Cezary Cybulski²⁹, Kamila Czene⁷⁵, Mary B Daly⁷⁶, Miguel de la Hoya⁵⁴, Kim De Leeneer⁶⁶, Joe Dennis¹³, Peter Devilee^{77

78}, Orland Diez^{79

80}, Susan M Domchek⁸¹, Thilo Dörk³⁷, Isabel Dos-Santos-Silva⁸², Alison M Dunning⁸³, Miriam Dwek⁸⁴, Diana M Eccles⁸⁵, Bent Ejlertsen⁸⁶, Carolina Ellberg⁸⁷, Christoph Engel^{88

89}, Mikael Eriksson⁷⁵, Peter A Fasching^{24

90}, Olivia Fletcher⁹¹, Henrik Flyger⁹², Florentia Fostira⁹³, Eitan Friedman^{94

95}, Lin Fritschi⁹⁶, Debra Frost¹³, Marike Gabrielson⁷⁵, Patricia A Ganz⁹⁷, Susan M Gapstur⁶⁰, Judy Garber⁹⁸, Montserrat García-Closas^{64

99

100}, José A García-Sáenz⁵⁴, Mia M Gaudet⁶⁰, Graham G Giles^{101

102}, Gord Glendon¹⁰, Andrew K Godwin¹⁰³, Mark S Goldberg^{104

105}, David E Goldgar¹⁰⁶, Anna González-Neira²⁷, Mark H Greene¹⁰⁷, Jacek Gronwald²⁹, Pascal Guénel¹⁰⁸, Christopher A Haiman¹⁰⁹, Per Hall^{75

110}, Ute Hamann¹¹¹, Christopher Hake¹¹², Wei He⁷⁵, Jane Heyworth¹¹³, Frans B L Hogervorst¹¹⁴, Antoinette Hollestelle¹¹⁵, Maartje J Hooning¹¹⁵, Robert N Hoover⁶⁴, John L Hopper¹⁰¹, Guanmengqian Huang¹¹¹, Peter J Hulick^{116

117}, Keith Humphreys⁷⁵, Evgeny N Imyanitov¹¹⁸; ABCTB Investigators¹¹⁹; HEBON Investigators¹²⁰; BCFR Investigators¹²¹; OCGN Investigators¹²²; Claudine Isaacs¹²³, Milena Jakimovska¹²⁴, Anna Jakubowska^{29

125}, Paul James^{57

126}, Ramunas Janavicius¹²⁷, Rachel C Jankowitz¹²⁸, Esther M John¹²¹, Nichola Johnson⁹¹, Vijai Joseph¹²⁹, Audrey Jung²⁵, Beth Y Karlan¹³⁰, Elza Khusnutdinova^{28

131}, Johanna I Kiiski¹³², Irene Konstantopoulou⁹³, Vessela N Kristensen^{133

134}, Yael Laitman⁹⁴, Diether Lambrechts^{34

35}, Conxi Lazaro¹³⁵, Dominique Leroux¹³⁶, Goska Leslie¹³, Jenny Lester¹³⁰, Fabienne Lesueur^{69

70

137}, Noralane Lindor¹³⁸, Sara Lindström^{139

140}, Wing-Yee Lo^{44

45}, Jennifer T Loud¹⁰⁷, Jan Lubiński²⁹, Enes Makalic¹⁰¹, Arto Mannermaa^{141

142

143}, Mehdi Manoochehri¹¹¹, Siranoush Manoukian²², Sara Margolin^{110

144}, John W M Martens¹¹⁵, Maria E Martinez^{145

146}, Laura Matricardi¹⁴⁷, Tabea Maurer⁶³, Dimitrios Mavroudis¹⁴⁸, Lesley McGuffog¹³, Alfons Meindl¹⁴⁹, Usha Menon¹⁵⁰, Kyriaki Michailidou^{13

151}, Pooja M Kapoor^{25

152}, Austin Miller¹⁵³, Marco Montagna¹⁴⁷, Fernando Moreno⁵⁴, Lidia Moserle¹⁴⁷, Anna M Mulligan^{154

155}, Taru A Muranen¹³², Katherine L Nathanson⁸¹, Susan L Neuhausen¹⁵⁶, Heli Nevanlinna¹³², Ines Nevelsteen¹⁵⁷, Finn C Nielsen¹⁵⁸, Liene Nikitina-Zake¹⁵⁹, Kenneth Offit^{129

160}, Edith Olah¹⁶¹, Olufunmilayo I Olopade¹⁶², Håkan Olsson⁸⁷, Ana Osorio^{26

27}, Janos Papp¹⁶¹, Tjoung-Won Park-Simon³⁷, Michael T Parsons¹⁶³, Inge S Pedersen¹⁶⁴, Ana Peixoto¹⁶⁵, Paolo Peterlongo¹⁶⁶, Julian Peto⁸², Paul D P Pharoah^{13

83}, Kelly-Anne Phillips^{56

57

101

167}, Dijana Plaseska-Karanfilska¹²⁴, Bruce Poppe⁶⁶, Nisha Pradhan¹²⁹, Karolina Prajzendanc²⁹, Nadege Presneau⁸⁴, Kevin Punie¹⁵⁷, Katri Pylkäs^{168

169}, Paolo Radice¹⁷⁰, Johanna Rantala¹⁷¹, Muhammad Usman Rashid^{111

172}, Gad Rennert⁸, Harvey A Risch¹⁷³, Mark Robson¹⁶⁰, Atocha Romero¹⁷⁴, Emmanouil Saloustros¹⁷⁵, Dale P Sandler¹⁷⁶, Catarina Santos¹⁶⁵, Elinor J Sawyer¹⁷⁷, Marjanka K Schmidt^{50

178}, Daniel F Schmidt^{101

179}, Rita K Schmutzler^{71

180}, Minouk J Schoemaker⁹⁹, Rodney J Scott^{181

182

183}, Priyanka Sharma¹⁸⁴, Xiao-Ou Shu⁷, Jacques Simard¹⁸⁵, Christian F Singer¹⁹, Anne-Bine Skytte¹⁸⁶, Penny Soucy¹⁸⁵, Melissa C Southey^{187

188}, John J Spinelli^{189

190}, Amanda B Spurdle¹⁶³, Jennifer Stone^{101

191}, Anthony J Swerdlow^{99

192}, William J Tapper¹⁹³, Jack A Taylor^{176

194}, Manuel R Teixeira^{165

195}, Mary Beth Terry¹⁹⁶, Alex Teulé¹⁹⁷, Mads Thomassen¹⁹⁸, Kathrin Thöne⁶³, Darcy L Thull¹⁹⁹, Marc Tischkowitz^{200

201}, Amanda E Toland²⁰², Rob A E M Tollenaar²⁰³, Diana Torres^{48

111}, Thérèse Truong¹⁰⁸, Nadine Tung²⁰⁴, Celine M Vachon²⁰⁵, Christi J van Asperen²⁰⁶, Ans M W van den Ouweland²⁰⁷, Elizabeth J van Rensburg²⁰⁸, Ana Vega^{26

30

31}, Alessandra Viel²⁰⁹, Paula Vieiro-Balo²¹⁰, Qin Wang¹³, Barbara Wappenschmidt^{71

180}, Clarice R Weinberg²¹¹, Jeffrey N Weitzel²¹², Camilla Wendt¹⁴⁴, Robert Winqvist^{168

169}, Xiaohong R Yang⁶⁴, Drakoulis Yannoukakos⁹³, Argyrios Ziogas¹², Roger L Milne^{100

101

187}, Douglas F Easton^{13

83}, Georgia Chenevix-Trench¹⁶³, Wei Zheng⁷, Peter Kraft^{1

2}, Xia Jiang^{1

2}

Affiliations

¹ Program in Genetic Epidemiology and Statistical Genetics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
² Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
³ Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
⁴ Dana-Farber Cancer Institute, Boston, Massachusetts.
⁵ UCLA Path & Lab Med, Los Angeles, California.
⁶ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
⁷ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
⁸ Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.
⁹ Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
¹⁰ Fred A, Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
¹¹ Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
¹² Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, California.
¹³ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹⁴ Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.
¹⁵ BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
¹⁶ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹⁷ Department of Public Health Sciences, and Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
¹⁸ Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
¹⁹ Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
²⁰ Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
²¹ Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin.
²² Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
²³ High Risk and Cancer Prevention Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
²⁴ Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
²⁵ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²⁶ Centro de Investigaci-n en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
²⁷ Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
²⁸ Institute of Biochemistry and Genetics, Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia.
²⁹ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
³⁰ Fundaci-n Pœblica Galega Medicina Xen-mica, Santiago De Compostela, Spain.
³¹ Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
³² Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
³³ Department of Oncology, University Hospital, Karolinska Institute, Stockholm, Sweden.
³⁴ VIB Center for Cancer Biology, VIB, Leuven, Belgium.
³⁵ Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, Belgium.
³⁶ Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
³⁷ Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
³⁸ NN Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
³⁹ Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
⁴⁰ Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
⁴¹ Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁴² Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy.
⁴³ Department of Oncology, Lund University and Skåne University Hospital, Lund, Sweden.
⁴⁴ Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
⁴⁵ iFIT-Cluster of Excellence, University of Tuebingen, Tuebingen, Germany.
⁴⁶ German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴⁷ Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
⁴⁸ Institute of Human Genetics, Pontificia Universidad Javeriana, Bogota, Colombia.
⁴⁹ Medical Faculty, Universidad de La Sabana, Bogota, Colombia.
⁵⁰ Division of Molecular Pathology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
⁵¹ Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany.
⁵² Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵³ Molecular Biology of Breast Cancer, University Womens Clinic Heidelberg, University of Heidelberg, Heidelberg, Germany.
⁵⁴ Medical Oncology Department, Hospital Cl'nico San Carlos, Instituto de Investigaci-n Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
⁵⁵ Section of Molecular Genetics, Dept, of Laboratory Medicine, University Hospital of Pisa, Pisa, Italy.
⁵⁶ Research Department, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
⁵⁷ Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
⁵⁸ Division of Molecular Carcinogenesis, The Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands.
⁵⁹ Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶⁰ Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
⁶¹ Department of Gynaecological Oncology, Chris OÕBrien Lifehouse and The University of Sydney, Camperdown, New South Wales, Australia.
⁶² Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, Vigo, Spain.
⁶³ Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁶⁴ Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
⁶⁵ Departments of Pediatrics and Medicine, Columbia University, New York, New York.
⁶⁶ Centre for Medical Genetics, Ghent University, Gent, Belgium.
⁶⁷ Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
⁶⁸ Department of Tumour Biology, INSERM U830, Paris, France.
⁶⁹ Institut Curie, Paris, France.
⁷⁰ Mines ParisTech, Fontainebleau, France.
⁷¹ Center for Hereditary Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
⁷² Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
⁷³ Department of Oncology and Metabolism, Sheffield Institute for Nucleic Acids (SInFoNiA), University of Sheffield, Sheffield, UK.
⁷⁴ Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
⁷⁵ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁷⁶ Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
⁷⁷ Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
⁷⁸ Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
⁷⁹ Hereditary Cancer Genetics Group, Area of Clinical and Molecular Genetics, Vall dHebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron, Barcelona, Spain.
⁸⁰ Clinical and Molecular Genetics Area, University Hospital Vall dHebron, Barcelona, Spain.
⁸¹ Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
⁸² Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
⁸³ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁸⁴ Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, UK.
⁸⁵ Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
⁸⁶ Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
⁸⁷ Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden.
⁸⁸ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
⁸⁹ LIFE - Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany.
⁹⁰ David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, California.
⁹¹ The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
⁹² Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
⁹³ Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritosဩ, Athens, Greece.
⁹⁴ The Susanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, Ramat Gan, Israel.
⁹⁵ Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
⁹⁶ School of Public Health, Curtin University, Perth, Western Australia, Australia.
⁹⁷ Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Centre, UCLA, Los Angeles, California.
⁹⁸ Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, Massachusetts.
⁹⁹ Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
¹⁰⁰ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
¹⁰¹ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
¹⁰² Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
¹⁰³ Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, Kanas.
¹⁰⁴ Department of Medicine, McGill University, Montreal, Quebec, Canada.
¹⁰⁵ Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
¹⁰⁶ Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah.
¹⁰⁷ Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
¹⁰⁸ Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France.
¹⁰⁹ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
¹¹⁰ Department of Oncology, Sšdersjukhuset, Stockholm, Sweden.
¹¹¹ Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹¹² City of Hope Clinical Cancer Genetics Community Research Network, Duarte, California.
¹¹³ School of Population and Global Health, The University of Western Australia, Perth, Western Australia, Australia.
¹¹⁴ Family Cancer Clinic, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
¹¹⁵ Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
¹¹⁶ Center for Medical Genetics, NorthShore University HealthSystem, Evanston, Illinois.
¹¹⁷ The University of Chicago Pritzker School of Medicine, Chicago, Illinois.
¹¹⁸ NN Petrov Institute of Oncology, St. Petersburg, Russia.
¹¹⁹ Australian Breast Cancer Tissue Bank, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
¹²⁰ The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Coordinating Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
¹²¹ Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California.
¹²² Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
¹²³ Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
¹²⁴ Research Centre for Genetic Engineering and Biotechnology 'Georgi D, Efremov', Macedonian Academy of Sciences and Arts, Skopje Republic of North Macedonia, North Macedonia.
¹²⁵ Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland.
¹²⁶ Parkville Familial Cancer Centre, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
¹²⁷ State Research Institute Innovative Medicine Center, Vilnius, Lithuania.
¹²⁸ Department of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
¹²⁹ Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York.
¹³⁰ David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California, Los Angeles, California.
¹³¹ Department of Genetics and Fundamental Medicine, Bashkir State Medical University, Ufa, Russia.
¹³² Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
¹³³ Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
¹³⁴ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
¹³⁵ Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Bellvitge Biomedical Research Institute, Catalan Institute of Oncology), CIBERONC, Barcelona, Spain.
¹³⁶ Departement de Ge netique, CHU de Grenoble, Grenoble, France.
¹³⁷ Genetic Epidemiology of Cancer Team, Inserm U900, Paris, France.
¹³⁸ Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona.
¹³⁹ Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.
¹⁴⁰ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
¹⁴¹ Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.
¹⁴² Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.
¹⁴³ Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
¹⁴⁴ Department of Clinical Science and Education, Sšdersjukhuset, Karolinska Institutet, Stockholm, Sweden.
¹⁴⁵ Moores Cancer Center, University of California San Diego, La Jolla, California.
¹⁴⁶ Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California.
¹⁴⁷ Immunology and Molecular Oncology Unit, Veneto Institute of Oncology ÊIOV-IRCCS, Padua, Italy.
¹⁴⁸ Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece.
¹⁴⁹ Department of Gynecology and Obstetrics, Ludwig Maximilian University of Munich, Munich, Germany.
¹⁵⁰ MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, University College London, London, UK.
¹⁵¹ Department of Electron Microscopy/Molecular Pathology and The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
¹⁵² Faculty of Medicine, University of Heidelberg, Heidelberg, Germany.
¹⁵³ NRG Oncology, Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, New York.
¹⁵⁴ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
¹⁵⁵ Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.
¹⁵⁶ Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California.
¹⁵⁷ Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
¹⁵⁸ Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁵⁹ Latvian Biomedical Research and Study Centre, Riga, Latvia.
¹⁶⁰ Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
¹⁶¹ Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.
¹⁶² Center for Clinical Cancer Genetics, The University of Chicago, Chicago, Illinois.
¹⁶³ Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
¹⁶⁴ Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
¹⁶⁵ Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
¹⁶⁶ Genome Diagnostics Program, IFOM-The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy.
¹⁶⁷ Department of Medicine Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
¹⁶⁸ Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland.
¹⁶⁹ Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland.
¹⁷⁰ Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
¹⁷¹ Clinical Genetics, Karolinska Institutet, Stockholm, Sweden.
¹⁷² Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan.
¹⁷³ Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
¹⁷⁴ Medical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain.
¹⁷⁵ Department of Oncology, University Hospital of Larissa, Larissa, Greece.
¹⁷⁶ Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina.
¹⁷⁷ Research Oncology, GuyÕs Hospital, King's College London, London, UK.
¹⁷⁸ Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
¹⁷⁹ Faculty of Information Technology, Monash University, Melbourne, Victoria, Australia.
¹⁸⁰ Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
¹⁸¹ Division of Molecular Medicine, Pathology North, John Hunter Hospital, Newcastle, New South Wales, Australia.
¹⁸² Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia.
¹⁸³ Hunter Medical Research Institute, John Hunter Hospital, Newcastle, New South Wales, Australia.
¹⁸⁴ Department of Internal Medicine, Division of Medical Oncology, University of Kansas Medical Center, Westwood, Kanas.
¹⁸⁵ Genomics Center, Centre Hospitalier Universitaire de Quebec-Universite Laval, Research Center, Quebec City, Qubec, Canada.
¹⁸⁶ Department of Clinical Genetics, Aarhus University Hospital, Aarhus N, Denmark.
¹⁸⁷ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
¹⁸⁸ Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
¹⁸⁹ Population Oncology, BC Cancer, Vancouver, British of Columbia, Canada.
¹⁹⁰ School of Population and Public Health, University of British Columbia, Vancouver, British of Columbia, Canada.
¹⁹¹ The Curtin UWA Centre for Genetic Origins of Health and Disease, Curtin University and University of Western Australia, Perth, Western Australia, Australia.
¹⁹² Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
¹⁹³ Faculty of Medicine, University of Southampton, Southampton, UK.
¹⁹⁴ Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina.
¹⁹⁵ Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.
¹⁹⁶ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
¹⁹⁷ Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, CIBERONC, Barcelona, Spain.
¹⁹⁸ Department of Clinical Genetics, Odense University Hospital, Odence C, Denmark.
¹⁹⁹ Department of Medicine, Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
²⁰⁰ Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montreal, Quebec, Canada.
²⁰¹ Department of Medical Genetics, University of Cambridge, Cambridge, UK.
²⁰² Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio.
²⁰³ Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
²⁰⁴ Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
²⁰⁵ Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
²⁰⁶ Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
²⁰⁷ Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
²⁰⁸ Department of Genetics, University of Pretoria, Arcadia, South Africa.
²⁰⁹ Division of Functional Onco-genomics and Genetics, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.
²¹⁰ Hospital Clínico Universitario (SERGAS), Universidad de Santiago de Compostela, CIMUS, Santiago de Compostela, España.
²¹¹ Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina.
²¹² Clinical Cancer Genomics, City of Hope, Duarte, California.

PMID: 32115800
PMCID: PMC7987299
DOI: 10.1002/gepi.22288

Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

Helian Feng et al. Genet Epidemiol. 2020 Jul.

. 2020 Jul;44(5):442-468.

doi: 10.1002/gepi.22288. Epub 2020 Mar 1.

Authors

Affiliations

¹ Program in Genetic Epidemiology and Statistical Genetics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
² Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
³ Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
⁴ Dana-Farber Cancer Institute, Boston, Massachusetts.
⁵ UCLA Path & Lab Med, Los Angeles, California.
⁶ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
⁷ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
⁸ Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.
⁹ Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
¹⁰ Fred A, Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
¹¹ Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
¹² Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, California.
¹³ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹⁴ Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.
¹⁵ BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
¹⁶ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹⁷ Department of Public Health Sciences, and Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
¹⁸ Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
¹⁹ Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
²⁰ Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
²¹ Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin.
²² Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
²³ High Risk and Cancer Prevention Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
²⁴ Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
²⁵ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²⁶ Centro de Investigaci-n en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
²⁷ Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
²⁸ Institute of Biochemistry and Genetics, Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia.
²⁹ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
³⁰ Fundaci-n Pœblica Galega Medicina Xen-mica, Santiago De Compostela, Spain.
³¹ Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
³² Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
³³ Department of Oncology, University Hospital, Karolinska Institute, Stockholm, Sweden.
³⁴ VIB Center for Cancer Biology, VIB, Leuven, Belgium.
³⁵ Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, Belgium.
³⁶ Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
³⁷ Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
³⁸ NN Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
³⁹ Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
⁴⁰ Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
⁴¹ Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁴² Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy.
⁴³ Department of Oncology, Lund University and Skåne University Hospital, Lund, Sweden.
⁴⁴ Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
⁴⁵ iFIT-Cluster of Excellence, University of Tuebingen, Tuebingen, Germany.
⁴⁶ German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴⁷ Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
⁴⁸ Institute of Human Genetics, Pontificia Universidad Javeriana, Bogota, Colombia.
⁴⁹ Medical Faculty, Universidad de La Sabana, Bogota, Colombia.
⁵⁰ Division of Molecular Pathology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
⁵¹ Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany.
⁵² Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵³ Molecular Biology of Breast Cancer, University Womens Clinic Heidelberg, University of Heidelberg, Heidelberg, Germany.
⁵⁴ Medical Oncology Department, Hospital Cl'nico San Carlos, Instituto de Investigaci-n Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
⁵⁵ Section of Molecular Genetics, Dept, of Laboratory Medicine, University Hospital of Pisa, Pisa, Italy.
⁵⁶ Research Department, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
⁵⁷ Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
⁵⁸ Division of Molecular Carcinogenesis, The Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands.
⁵⁹ Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶⁰ Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
⁶¹ Department of Gynaecological Oncology, Chris OÕBrien Lifehouse and The University of Sydney, Camperdown, New South Wales, Australia.
⁶² Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, Vigo, Spain.
⁶³ Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁶⁴ Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
⁶⁵ Departments of Pediatrics and Medicine, Columbia University, New York, New York.
⁶⁶ Centre for Medical Genetics, Ghent University, Gent, Belgium.
⁶⁷ Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
⁶⁸ Department of Tumour Biology, INSERM U830, Paris, France.
⁶⁹ Institut Curie, Paris, France.
⁷⁰ Mines ParisTech, Fontainebleau, France.
⁷¹ Center for Hereditary Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
⁷² Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
⁷³ Department of Oncology and Metabolism, Sheffield Institute for Nucleic Acids (SInFoNiA), University of Sheffield, Sheffield, UK.
⁷⁴ Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
⁷⁵ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁷⁶ Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
⁷⁷ Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
⁷⁸ Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
⁷⁹ Hereditary Cancer Genetics Group, Area of Clinical and Molecular Genetics, Vall dHebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron, Barcelona, Spain.
⁸⁰ Clinical and Molecular Genetics Area, University Hospital Vall dHebron, Barcelona, Spain.
⁸¹ Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
⁸² Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
⁸³ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁸⁴ Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, UK.
⁸⁵ Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
⁸⁶ Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
⁸⁷ Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden.
⁸⁸ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
⁸⁹ LIFE - Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany.
⁹⁰ David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, California.
⁹¹ The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
⁹² Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
⁹³ Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritosဩ, Athens, Greece.
⁹⁴ The Susanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, Ramat Gan, Israel.
⁹⁵ Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
⁹⁶ School of Public Health, Curtin University, Perth, Western Australia, Australia.
⁹⁷ Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Centre, UCLA, Los Angeles, California.
⁹⁸ Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, Massachusetts.
⁹⁹ Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
¹⁰⁰ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
¹⁰¹ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
¹⁰² Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
¹⁰³ Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, Kanas.
¹⁰⁴ Department of Medicine, McGill University, Montreal, Quebec, Canada.
¹⁰⁵ Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
¹⁰⁶ Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah.
¹⁰⁷ Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
¹⁰⁸ Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France.
¹⁰⁹ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
¹¹⁰ Department of Oncology, Sšdersjukhuset, Stockholm, Sweden.
¹¹¹ Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹¹² City of Hope Clinical Cancer Genetics Community Research Network, Duarte, California.
¹¹³ School of Population and Global Health, The University of Western Australia, Perth, Western Australia, Australia.
¹¹⁴ Family Cancer Clinic, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
¹¹⁵ Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
¹¹⁶ Center for Medical Genetics, NorthShore University HealthSystem, Evanston, Illinois.
¹¹⁷ The University of Chicago Pritzker School of Medicine, Chicago, Illinois.
¹¹⁸ NN Petrov Institute of Oncology, St. Petersburg, Russia.
¹¹⁹ Australian Breast Cancer Tissue Bank, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
¹²⁰ The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Coordinating Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
¹²¹ Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California.
¹²² Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
¹²³ Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
¹²⁴ Research Centre for Genetic Engineering and Biotechnology 'Georgi D, Efremov', Macedonian Academy of Sciences and Arts, Skopje Republic of North Macedonia, North Macedonia.
¹²⁵ Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland.
¹²⁶ Parkville Familial Cancer Centre, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
¹²⁷ State Research Institute Innovative Medicine Center, Vilnius, Lithuania.
¹²⁸ Department of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
¹²⁹ Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York.
¹³⁰ David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California, Los Angeles, California.
¹³¹ Department of Genetics and Fundamental Medicine, Bashkir State Medical University, Ufa, Russia.
¹³² Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
¹³³ Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
¹³⁴ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
¹³⁵ Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Bellvitge Biomedical Research Institute, Catalan Institute of Oncology), CIBERONC, Barcelona, Spain.
¹³⁶ Departement de Ge netique, CHU de Grenoble, Grenoble, France.
¹³⁷ Genetic Epidemiology of Cancer Team, Inserm U900, Paris, France.
¹³⁸ Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona.
¹³⁹ Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.
¹⁴⁰ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
¹⁴¹ Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.
¹⁴² Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.
¹⁴³ Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
¹⁴⁴ Department of Clinical Science and Education, Sšdersjukhuset, Karolinska Institutet, Stockholm, Sweden.
¹⁴⁵ Moores Cancer Center, University of California San Diego, La Jolla, California.
¹⁴⁶ Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California.
¹⁴⁷ Immunology and Molecular Oncology Unit, Veneto Institute of Oncology ÊIOV-IRCCS, Padua, Italy.
¹⁴⁸ Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece.
¹⁴⁹ Department of Gynecology and Obstetrics, Ludwig Maximilian University of Munich, Munich, Germany.
¹⁵⁰ MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, University College London, London, UK.
¹⁵¹ Department of Electron Microscopy/Molecular Pathology and The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
¹⁵² Faculty of Medicine, University of Heidelberg, Heidelberg, Germany.
¹⁵³ NRG Oncology, Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, New York.
¹⁵⁴ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
¹⁵⁵ Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.
¹⁵⁶ Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California.
¹⁵⁷ Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
¹⁵⁸ Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁵⁹ Latvian Biomedical Research and Study Centre, Riga, Latvia.
¹⁶⁰ Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
¹⁶¹ Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.
¹⁶² Center for Clinical Cancer Genetics, The University of Chicago, Chicago, Illinois.
¹⁶³ Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
¹⁶⁴ Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
¹⁶⁵ Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
¹⁶⁶ Genome Diagnostics Program, IFOM-The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy.
¹⁶⁷ Department of Medicine Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
¹⁶⁸ Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland.
¹⁶⁹ Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland.
¹⁷⁰ Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
¹⁷¹ Clinical Genetics, Karolinska Institutet, Stockholm, Sweden.
¹⁷² Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan.
¹⁷³ Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
¹⁷⁴ Medical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain.
¹⁷⁵ Department of Oncology, University Hospital of Larissa, Larissa, Greece.
¹⁷⁶ Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina.
¹⁷⁷ Research Oncology, GuyÕs Hospital, King's College London, London, UK.
¹⁷⁸ Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
¹⁷⁹ Faculty of Information Technology, Monash University, Melbourne, Victoria, Australia.
¹⁸⁰ Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
¹⁸¹ Division of Molecular Medicine, Pathology North, John Hunter Hospital, Newcastle, New South Wales, Australia.
¹⁸² Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia.
¹⁸³ Hunter Medical Research Institute, John Hunter Hospital, Newcastle, New South Wales, Australia.
¹⁸⁴ Department of Internal Medicine, Division of Medical Oncology, University of Kansas Medical Center, Westwood, Kanas.
¹⁸⁵ Genomics Center, Centre Hospitalier Universitaire de Quebec-Universite Laval, Research Center, Quebec City, Qubec, Canada.
¹⁸⁶ Department of Clinical Genetics, Aarhus University Hospital, Aarhus N, Denmark.
¹⁸⁷ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
¹⁸⁸ Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
¹⁸⁹ Population Oncology, BC Cancer, Vancouver, British of Columbia, Canada.
¹⁹⁰ School of Population and Public Health, University of British Columbia, Vancouver, British of Columbia, Canada.
¹⁹¹ The Curtin UWA Centre for Genetic Origins of Health and Disease, Curtin University and University of Western Australia, Perth, Western Australia, Australia.
¹⁹² Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
¹⁹³ Faculty of Medicine, University of Southampton, Southampton, UK.
¹⁹⁴ Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina.
¹⁹⁵ Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.
¹⁹⁶ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
¹⁹⁷ Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, CIBERONC, Barcelona, Spain.
¹⁹⁸ Department of Clinical Genetics, Odense University Hospital, Odence C, Denmark.
¹⁹⁹ Department of Medicine, Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
²⁰⁰ Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montreal, Quebec, Canada.
²⁰¹ Department of Medical Genetics, University of Cambridge, Cambridge, UK.
²⁰² Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio.
²⁰³ Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
²⁰⁴ Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
²⁰⁵ Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
²⁰⁶ Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
²⁰⁷ Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
²⁰⁸ Department of Genetics, University of Pretoria, Arcadia, South Africa.
²⁰⁹ Division of Functional Onco-genomics and Genetics, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.
²¹⁰ Hospital Clínico Universitario (SERGAS), Universidad de Santiago de Compostela, CIMUS, Santiago de Compostela, España.
²¹¹ Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina.
²¹² Clinical Cancer Genomics, City of Hope, Duarte, California.

PMID: 32115800
PMCID: PMC7987299
DOI: 10.1002/gepi.22288

Abstract

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.

Keywords: GWAS; TWAS; breast cancer subtype; causal gene.

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Figures

**FIGURE 1**
Scatter plot comparing the transcriptome-wide association study z scores in ER+ and ER− patients

**FIGURE 2**
Conditional and joint analysis (COJO) for genes near a strong breast cancer GWAS hit. (a) COJO results adjusting for predicted expression of *ALS2CR12*. After conditioning on *ALS2CR12*, almost all original significant GWAS signals (grey dots) disappear (blue dots). (b) COJO results adjusting for the predicted expression of *CASP8*. After conditioning on *CASP8,* some of the original GWAS significant signals (grey dots) remains (blue dots)

**FIGURE 3**
COJO for regions with multiple TWAS associations. For each plot, the top panel shows all genes in the locus. After COJO analysis, the marginally associated genes are highlighted in blue, while those that remain jointly significant are highlighted in green (in this case, *L3MBTL3*, *CASP8*, and *ALS2C12*). The bottom panel shows a Manhattan plot of the GWAS signals before (gray) and after (blue) conditioning on the significant (green) genes. (a) COJO results for 6q22 (only one gene remains significant after COJO). (b) COJO results for 2q33 (an example of multiple genes remaining jointly remain significant after COJO). COJO, conditional and joint analysis; GWAS, genome-wide association studies; TWAS, transcriptome-wide association studies

See this image and copyright information in PMC

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Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

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Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

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