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Br J Cancer. 2019 Mar;120(6):647-657. doi: 10.1038/s41416-019-0393-x. Epub 2019 Feb 21.

Genome-wide association study of germline variants and breast cancer-specific mortality.

Escala-Garcia M1, Guo Q2, Dörk T3, Canisius S1,4, Keeman R1, Dennis J5, Beesley J6, Lecarpentier J5, Bolla MK5, Wang Q5, Abraham J7,8,9, Andrulis IL10,11, Anton-Culver H12, Arndt V13, Auer PL14,15, Beckmann MW16, Behrens S17, Benitez J18,19, Bermisheva M20, Bernstein L21, Blomqvist C22,23, Boeckx B24,25, Bojesen SE26,27,28, Bonanni B29, Børresen-Dale AL30,31,32,33,34,35,36,37,38,39, Brauch H40,41,42, Brenner H13,42,43, Brentnall A44, Brinton L45, Broberg P46, Brock IW47, Brucker SY48, Burwinkel B49,50, Caldas C8,9,51, Caldés T52, Campa D17,53, Canzian F50, Carracedo A54,55,56, Carter BD57, Castelao JE58, Chang-Claude J17,59, Chanock SJ45, Chenevix-Trench G6, Cheng TD60, Chin SF61, Clarke CL62; NBCS Collaborators, Cordina-Duverger E63, Couch FJ64, Cox DG65,66, Cox A47, Cross SS67, Czene K68, Daly MB69, Devilee P70,71, Dunn JA72, Dunning AM7, Durcan L73,74, Dwek M75, Earl HM9,76, Ekici AB77, Eliassen AH78,79, Ellberg C46, Engel C80,81, Eriksson M68, Evans DG82,83, Figueroa J45,84,85, Flesch-Janys D86,87, Flyger H88, Gabrielson M68, Gago-Dominguez M54,89, Galle E24,25, Gapstur SM57, García-Closas M45,90, García-Sáenz JA52, Gaudet MM57, George A91,92, Georgoulias V93, Giles GG94,95,96, Glendon G10, Goldgar DE97, González-Neira A18, Alnæs GIG30, Grip M98, Guénel P63, Haeberle L99, Hahnen E100,101, Haiman CA102, Håkansson N103, Hall P68,104, Hamann U105, Hankinson S106, Harkness EF107,108,109, Harrington PA7, Hart SN110, Hartikainen JM111,112,113, Hein A16, Hillemanns P3, Hiller L72, Holleczek B114, Hollestelle A115, Hooning MJ115, Hoover RN45, Hopper JL95, Howell A116, Huang G105, Humphreys K68, Hunter DJ79,117,118, Janni W85, John EM119,120,121, Jones ME90, Jukkola-Vuorinen A122, Jung A17, Kaaks R17, Kabisch M105, Kaczmarek K123, Kerin MJ124, Khan S125, Khusnutdinova E20,126, Kiiski JI125, Kitahara CM127, Knight JA128,129, Ko YD130, Koppert LB131, Kosma VM111,112,113, Kraft P79,117, Kristensen VN30,31,32,33,34,35,36,37,38,39, Krüger U46, Kühl T59, Lambrechts D24,25, Le Marchand L132, Lee E102, Lejbkowicz F133, Li L134, Lindblom A135, Lindström S136,137, Linet M127, Lissowska J138, Lo WY40,41, Loibl S139, Lubiński J123, Lux MP99, MacInnis RJ94,95, Maierthaler M50, Maishman T73,74, Makalic E95, Mannermaa A111,112,113, Manoochehri M105, Manoukian S140, Margolin S141, Martinez ME89,142, Mavroudis D93, McLean C143, Meindl A144, Middha P17,145, Miller N124, Milne RL94,95, Moreno F52, Mulligan AM146,147, Mulot C148, Nassir R149, Neuhausen SL21, Newman WT82,83, Nielsen SF26,27, Nordestgaard BG26,27,28, Norman A110, Olsson H46, Orr N150, Pankratz VS151, Park-Simon TW3, Perez JIA152, Pérez-Barrios C153, Peterlongo P154, Petridis C155, Pinchev M133, Prajzendanc K123, Prentice R14, Presneau N75, Prokofieva D126, Pylkäs K156,157, Rack B144, Radice P158, Ramachandran D3, Rennert G133, Rennert HS133, Rhenius V7, Romero A153, Roylance R159, Saloustros E160, Sawyer EJ155, Schmidt DF95, Schmutzler RK100,101, Schneeweiss A49,161, Schoemaker MJ91, Schumacher F162, Schwentner L85, Scott RJ163,164,165,166, Scott C110, Seynaeve C115, Shah M7, Simard J167, Smeets A168, Sohn C161, Southey MC169,170, Swerdlow AJ91,171, Talhouk A172,173,174, Tamimi RM78,79,117, Tapper WJ175, Teixeira MR176,177, Tengström M111,178,179, Terry MB180, Thöne K59, Tollenaar RAEM181, Tomlinson I182,183, Torres D105,184, Truong T63, Turman C79, Turnbull C91, Ulmer HU185, Untch M186, Vachon C110, van Asperen CJ187, van den Ouweland AMW188, van Veen EM82,83, Wendt C189, Whittemore AS120,121, Willett W79,190,191, Winqvist R156,157, Wolk A192, Yang XR45, Zhang Y13,42, Easton DF5,7, Fasching PA16,193, Nevanlinna H125, Eccles DM74, Pharoah PDP5,7, Schmidt MK1,194.

Author information

1
The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam, The Netherlands.
2
University of Cambridge, Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, Cambridge, UK. qg209@medschl.cam.ac.uk.
3
Hannover Medical School, Gynaecology Research Unit, Hannover, Germany.
4
The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Division of Molecular Carcinogenesis, Amsterdam, The Netherlands.
5
University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK.
6
QIMR Berghofer Medical Research Institute, Department of Genetics and Computational Biology, Brisbane, Queensland, Australia.
7
University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, UK.
8
Cambridge Experimental Cancer Medicine Centre, Cambridge, UK.
9
University of Cambridge NHS Foundation Hospitals, Cambridge Breast Unit and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
10
Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Fred A. Litwin Center for Cancer Genetics, Toronto, ON, Canada.
11
University of Toronto, Department of Molecular Genetics, Toronto, ON, Canada.
12
University of California Irvine, Department of Epidemiology, Genetic Epidemiology Research Institute, Irvine, CA, USA.
13
German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany.
14
Fred Hutchinson Cancer Research Center, Cancer Prevention Program, Seattle, WA, USA.
15
University of Wisconsin-Milwaukee, Zilber School of Public Health, Milwaukee, WI, USA.
16
University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, Erlangen, Germany.
17
German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany.
18
Spanish National Cancer Research Centre (CNIO), Human Cancer Genetics Programme, Madrid, Spain.
19
Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
20
Ufa Scientific Center of Russian Academy of Sciences, Institute of Biochemistry and Genetics, Ufa, Russia.
21
Beckman Research Institute of City of Hope, Department of Population Sciences, Duarte, CA, USA.
22
University of Helsinki, Department of Oncology, Helsinki University Hospital, Helsinki, Finland.
23
Örebro University Hospital, Department of Oncology, Örebro, Sweden.
24
VIB, VIB Center for Cancer Biology, Leuven, Belgium.
25
University of Leuven, Laboratory for Translational Genetics, Department of Human Genetics, Leuven, Belgium.
26
Copenhagen University Hospital, Copenhagen General Population Study, Herlevand Gentofte Hospital, Herlev, Denmark.
27
Copenhagen University Hospital, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Herlev, Denmark.
28
University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark.
29
Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS Milan, Milan, 20141, Italy.
30
Oslo University Hospital-Radiumhospitalet, Department of Cancer Genetics, Institute for Cancer Research, Oslo, Norway.
31
University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo, Norway.
32
Department of Research, Vestre Viken Hospital, Drammen, Norway; Section for Breast- and Endocrine Surgery, Department of Cancer, Division of Surgery, Cancer and Transplantation Medicine, Oslo University Hospital-Ullevål, Oslo, Norway.
33
Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
34
Department of Pathology at Akershus University hospital, Lørenskog, Norway.
35
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
36
Department of Oncology, Division of Surgery and Cancer and Transplantation Medicine, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
37
National Advisory Unit on Late Effects after Cancer Treatment, Department of Oncology, Oslo University Hospital, Oslo, Norway.
38
Department of Oncology, Akershus University Hospital, Lørenskog, Norway.
39
Breast Cancer Research Consortium, Oslo University Hospital, Oslo, Norway.
40
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
41
University of Tübingen, Tübingen, Germany.
42
German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
43
German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Division of Preventive Oncology, Heidelberg, Germany.
44
Queen Mary University of London, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, London, UK.
45
National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA.
46
Lund University, Department of Cancer Epidemiology, Clinical Sciences, Lund, Sweden.
47
University of Sheffield, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, Sheffield, UK.
48
University of Tübingen, Department of Gynecology and Obstetrics, Tübingen, Germany.
49
University of Heidelberg, Department of Obstetrics and Gynecology, Heidelberg, Germany.
50
German Cancer Research Center (DKFZ), Molecular Epidemiology Group, C080, Heidelberg, Germany.
51
The Institute of Cancer Research, Section of Cancer Genetics, London, UK.
52
Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Medical Oncology Department, Hospital Cl'nico San Carlos, Madrid, Spain.
53
University of Pisa, Department of Biology, Pisa, Italy.
54
Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Genomic Medicine Group, Galician Foundation of Genomic Medicine, SERGAS, Santiago de Compostela, Spain.
55
Universidad de Santiago de Compostela, Centro de Investigación en Red de Enfermedades Raras (CIBERER), Santiago De Compostela, Spain.
56
King Abdulaziz University, Center of Excellence in Genomic Medicine, Jeddah, Kingdom of Saudi Arabia.
57
American Cancer Society, Epidemiology Research Program, Atlanta, GA, USA.
58
Instituto de Investigación Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, Oncology and Genetics Unit, Vigo, Spain.
59
University Medical Center Hamburg-Eppendorf, Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), Hamburg, Germany.
60
Roswell Park Cancer Institute, Division of Cancer Prevention and Control, Buffalo, NY, USA.
61
University of Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK.
62
University of Sydney, Westmead Institute for Medical Research, Sydney, NSW, Australia.
63
INSERM, University Paris-Sud, University Paris-Saclay, Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), Villejuif, France.
64
Mayo Clinic, Department of Laboratory Medicine and Pathology, Rochester, MN, USA.
65
Imperial College London, Department of Epidemiology and Biostatistics, School of Public Health, London, UK.
66
Cancer Research Center of Lyon, INSERM U1052, Lyon, France.
67
University of Sheffield, Academic Unit of Pathology, Department of Neuroscience, Sheffield, UK.
68
Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
69
Fox Chase Cancer Center, Department of Clinical Genetics, Philadelphia, PA, USA.
70
Leiden University Medical Center, Department of Pathology, Leiden, The Netherlands.
71
Leiden University Medical Center, Department of Human Genetics, Leiden, The Netherlands.
72
University of Warwick, Warwick Clinical Trials Unit, Coventry, UK.
73
University of Southampton, Southampton Clinical Trials Unit, Faculty of Medicine, Southampton, UK.
74
University of Southampton, Cancer Sciences Academic Unit, Faculty of Medicine, Southampton, UK.
75
University of Westminster, Department of Biomedical Sciences, Faculty of Science and Technology, London, UK.
76
University of Cambridge, Department of Oncology, Cambridge, UK.
77
Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Institute of Human Genetics, University Hospital Erlangen, Erlangen, Germany.
78
Harvard Medical School, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
79
Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, MA, USA.
80
University of Leipzig, Institute for Medical Informatics, Statistics and Epidemiology, Leipzig, Germany.
81
University of Leipzig, LIFE - Leipzig Research Centre for Civilization Diseases, Leipzig, Germany.
82
University of Manchester, Manchester Academic Health Science Centre, Division of Evolution and Genomic Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester, UK.
83
St Marys Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester Centre for Genomic Medicine, Manchester, UK.
84
The University of Edinburgh Medical School, Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK.
85
Cancer Research UK Edinburgh Centre, Edinburgh, UK.
86
University Medical Centre Hamburg-Eppendorf, Institute for Medical Biometrics and Epidemiology, Hamburg, Germany.
87
University Medical Centre Hamburg-Eppendorf, Department of Cancer Epidemiology, Clinical Cancer Registry, Hamburg, Germany.
88
Copenhagen University Hospital, Department of Breast Surgery, Herlev and Gentofte Hospital, Herlev, Denmark.
89
University of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
90
Institute of Cancer Research, Division of Genetics and Epidemiology, London, UK.
91
The Institute of Cancer Research, Division of Genetics and Epidemiology, London, UK.
92
The Royal Marsden NHS Foundation Trust, Cancer Genetics Unit, London, UK.
93
University Hospital of Heraklion, Department of Medical Oncology, Heraklion, Greece.
94
Cancer Council Victoria, Cancer Epidemiology & Intelligence Division, Melbourne, VIC, Australia.
95
The University of Melbourne, Melbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, Melbourne, VIC, Australia.
96
Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, VIC, Australia.
97
Huntsman Cancer Institute, University of Utah School of Medicine, Department of Dermatology, Salt Lake City, UT, USA.
98
University of Oulu, Department of Surgery, Oulu University Hospital, Oulu, Finland.
99
Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Centre Erlangen-EMN, Department of Gynaecology and Obstetrics, University Hospital Erlangen, Erlangen, Germany.
100
University Hospital of Cologne, Centre for Hereditary Breast and Ovarian Cancer, Cologne, Germany.
101
University of Cologne, Centre for Molecular Medicine Cologne (CMMC), Cologne, Germany.
102
University of Southern California, Department of Preventive Medicine, Keck School of Medicine, Los Angeles, CA, USA.
103
Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden.
104
South General Hospital, Department of Oncology, Stockholm, Sweden.
105
German Cancer Research Centre (DKFZ), Molecular Genetics of Breast Cancer, Heidelberg, Germany.
106
University of Massachusetts, Amherst, Department of Biostatistics & Epidemiology, Amherst, MA, USA.
107
University of Manchester, Manchester Academic Health Science Centre, Division of Informatics, Imaging and Data Sciences, Faculty of Biology, Medicine and Health, Manchester, UK.
108
Wythenshawe Hospital, Manchester University NHS Foundation Trust, Nightingale Breast Screening Centre, Manchester, UK.
109
Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Unit, Manchester, UK.
110
Mayo Clinic, Department of Health Sciences Research, Rochester, MN, USA.
111
University of Eastern Finland, Translational Cancer Research Area, Kuopio, Finland.
112
University of Eastern Finland, Institute of Clinical Medicine, Pathology and Forensic Medicine, Kuopio, Finland.
113
Kuopio University Hospital, Imaging Centre, Department of Clinical Pathology, Kuopio, Finland.
114
Saarland Cancer Registry, Saarbruecken, Germany.
115
Erasmus MC Cancer Institute, Department of Medical Oncology, Family Cancer Clinic, Rotterdam, The Netherlands.
116
University of Manchester, Institute of Cancer studies, Manchester, UK.
117
Harvard T.H. Chan School of Public Health, Program in Genetic Epidemiology and Statistical Genetics, Boston, MA, USA.
118
University of Oxford, Nuffield Department of Population Health, Oxford, UK.
119
Cancer Prevention Institute of California, Department of Epidemiology, Fremont, CA, USA.
120
Stanford University School of Medicine, Department of Health Research and Policy - Epidemiology, Stanford, CA, USA.
121
Stanford University School of Medicine, Department of Biomedical Data Science, Stanford, CA, USA.
122
Tampere University Hospital, Department of Oncology, Tampere, Finland.
123
Pomeranian Medical University, Department of Genetics and Pathology, Szczecin, Poland.
124
National University of Ireland, Surgery, School of Medicine, Galway, Ireland.
125
University of Helsinki, Department of Obstetrics and Gynaecology, Helsinki University Hospital, Helsinki, Finland.
126
Bashkir State University, Department of Genetics and Fundamental Medicine, Ufa, Russia.
127
National Cancer Institute, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA.
128
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Prosserman Centre for Population Health Research, Toronto, ON, Canada.
129
University of Toronto, Division of Epidemiology, Dalla Lana School of Public Health, Toronto, ON, Canada.
130
Johanniter Krankenhaus, Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Bonn, Germany.
131
Erasmus MC Cancer Institute, Department of Surgical Oncology, Family Cancer Clinic, Rotterdam, The Netherlands.
132
University of Hawaii Cancer Center, Epidemiology Program, Honolulu, HI, USA.
133
Carmel Medical Center and Technion Faculty of Medicine, Clalit National Cancer Control Center, Haifa, Israel.
134
Tianjin Medical University Cancer Institute and Hospital, Department of Epidemiology, Tianjin, China.
135
Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden.
136
University of Washington School of Public Health, Department of Epidemiology, Seattle, WA, USA.
137
Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA, USA.
138
M. Sklodowska-Curie Cancer Centre, Oncology Institute, Department of Cancer Epidemiology and Prevention, Warsaw, Poland.
139
GmbH, German Breast Group, Neu Isenburg, Germany.
140
Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT), Unit of Medical Genetics, Department of Medical Oncology and Haematology, Milan, Italy.
141
Karolinska Institutet, Department of Clinical Science and Education, Sšdersjukhuset, Stockholm, Sweden.
142
University of California San Diego, Department of Family Medicine and Public Health, La Jolla, CA, USA.
143
The Alfred Hospital, Anatomical Pathology, Melbourne, VIC, Australia.
144
Ludwig Maximilian University of Munich, Department of Gynaecology and Obstetrics, Munich, Germany.
145
University of Heidelberg, Faculty of Medicine, Heidelberg, Germany.
146
University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, ON, Canada.
147
University Health Network, Laboratory Medicine Program, Toronto, ON, Canada.
148
INSERM UMR-S1147, Université Paris Sorbonne Cité, Paris, France.
149
University of California Davis, Department of Biochemistry and Molecular Medicine, Davis, CA, USA.
150
Queen's University Belfast, Centre for Cancer Research and Cell Biology, Belfast, Ireland, UK.
151
University of New Mexico, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
152
Hospital Monte Naranco, Servicio de Cirug'a General y Especialidades, Oviedo, Spain.
153
Hospital Universitario Puerta de Hierro, Medical Oncology Department, Madrid, Spain.
154
The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, IFOM, Milan, Italy.
155
King's College London, Research Oncology, Guy's Hospital, London, UK.
156
University of Oulu, Laboratory of Cancer Genetics and Tumour Biology, Cancer and Translational Medicine Research Unit, Biocentre Oulu, Oulu, Finland.
157
Northern Finland Laboratory Centre Oulu, Laboratory of Cancer Genetics and Tumour Biology, Oulu, Finland.
158
Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT), Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Milan, Italy.
159
UCLH Foundation Trust, Department of Oncology, London, UK.
160
University Hospital of Larissa, Department of Oncology, Larissa, Greece.
161
University of Heidelberg, National Centre for Tumour Diseases, Heidelberg, Germany.
162
Case Western Reserve University, Department of Population and Quantitative Health Sciences, Cleveland, OH, USA.
163
John Hunter Hospital, Division of Molecular Medicine, Pathology North, Newcastle, NSW, Australia.
164
University of Newcastle, Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health, Callaghan, NSW, Australia.
165
John Hunter Hospital, Hunter Medical Research Institute, Newcastle, NSW, Australia.
166
University of Newcastle, Centre for Information Based Medicine, Callaghan, Newcastle, NSW, Australia.
167
Centre Hospitalier Universitaire de Québec - Université Laval Research Centre, Genomics Centre, Québec City, QC, Canada.
168
University Hospitals Leuven, Department of Surgical Oncology, Leuven, Belgium.
169
Monash University, Precision Medicine, School of Clinical Sciences at Monash Health, Clayton, Victoria, Australia.
170
The University of Melbourne, Department of Clinical Pathology, Melbourne, VIC, Australia.
171
The Institute of Cancer Research, Division of Breast Cancer Research, London, UK.
172
BC Cancer Agency and University of British Columbia, British Columbia's Ovarian Cancer Research (OVCARE) Program, Vancouver General Hospital, Vancouver, BC, Canada.
173
University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, BC, Canada.
174
University of British Columbia, Department of Obstetrics and Gynaecology, Vancouver, BC, Canada.
175
University of Southampton, Faculty of Medicine, Southampton, UK.
176
Portuguese Oncology Institute, Department of Genetics, Porto, Portugal.
177
University of Porto, Biomedical Sciences Institute (ICBAS), Porto, Portugal.
178
Kuopio University Hospital, Cancer Centre, Kuopio, Finland.
179
University of Eastern Finland, Institute of Clinical Medicine, Oncology, Kuopio, Finland.
180
Columbia University, Department of Epidemiology, Mailman School of Public Health, New York, NY, USA.
181
Leiden University Medical Centre, Department of Surgery, Leiden, The Netherlands.
182
University of Birmingham, Institute of Cancer and Genomic Sciences, Birmingham, UK.
183
University of Oxford, Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, Oxford, UK.
184
Pontificia Universidad Javeriana, Institute of Human Genetics, Bogota, Colombia.
185
Frauenklinik der Stadtklinik Baden-Baden, Baden-Baden, Germany.
186
Helios Clinics Berlin-Buch, Department of Gynaecology and Obstetrics, Berlin, Germany.
187
Leiden University Medical Centre, Department of Clinical Genetics, Leiden, The Netherlands.
188
Erasmus University Medical Centre, Department of Clinical Genetics, Rotterdam, The Netherlands.
189
Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, Stockholm, Sweden.
190
Harvard T.H. Chan School of Public Health, Department of Nutrition, Boston, MA, USA.
191
Brigham and Women's Hospital and Harvard Medical School, Channing Division of Network Medicine, Boston, MA, USA.
192
Karolinska Institutet, Department of Environmental Medicine, Division of Nutritional Epidemiology, Stockholm, Sweden.
193
University of California at Los Angeles, David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, Los Angeles, CA, USA.
194
The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Division of Psychosocial Research and Epidemiology, Amsterdam, The Netherlands.

Abstract

BACKGROUND:

We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry.

METHODS:

Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP).

RESULTS:

We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10-8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10-7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84-0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10-7, HR = 1.27, 95% CI = 1.16-1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster.

CONCLUSIONS:

We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients.

PMID:
30787463
DOI:
10.1038/s41416-019-0393-x
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