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Nat Commun. 2019 Apr 15;10(1):1741. doi: 10.1038/s41467-018-08053-5.

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.

Ferreira MA1, Gamazon ER2,3, Al-Ejeh F4, Aittomäki K5, Andrulis IL6,7, Anton-Culver H8, Arason A9,10, Arndt V11, Aronson KJ12, Arun BK13, Asseryanis E14, Azzollini J15, Balmaña J16,17, Barnes DR18, Barrowdale D18, Beckmann MW19, Behrens S20, Benitez J21,22, Bermisheva M23, Białkowska K24, Blomqvist C25,26, Bogdanova NV27,28,29, Bojesen SE30,31,32, Bolla MK18, Borg A33, Brauch H34,35,36, Brenner H11,36,37, Broeks A38, Burwinkel B39,40, Caldés T41, Caligo MA42, Campa D20,43, Campbell I44,45, Canzian F46, Carter J47, Carter BD48, Castelao JE49, Chang-Claude J20,50, Chanock SJ51, Christiansen H27, Chung WK52, Claes KBM53, Clarke CL54; EMBRACE Collaborators; GC-HBOC Study Collaborators; GEMO Study Collaborators, Couch FJ55, Cox A56, Cross SS57, Czene K58, Daly MB59, de la Hoya M41, Dennis J18, Devilee P60,61, Diez O16,62, Dörk T28, Dunning AM63, Dwek M64, Eccles DM65, Ejlertsen B66, Ellberg C67, Engel C68, Eriksson M58, Fasching PA19,69, Fletcher O70, Flyger H71, Friedman E72,73, Frost D18, Gabrielson M58, Gago-Dominguez M74,75, Ganz PA76, Gapstur SM48, Garber J77, García-Closas M51,78, García-Sáenz JA79, Gaudet MM48, Giles GG80,81,82, Glendon G6, Godwin AK83, Goldberg MS84,85, Goldgar DE86, González-Neira A22, Greene MH87, Gronwald J24, Guénel P88, Haiman CA89, Hall P58,90, Hamann U91, He W58, Heyworth J92, Hogervorst FBL93, Hollestelle A94, Hoover RN51, Hopper JL81, Hulick PJ95,96, Humphreys K58, Imyanitov EN97; ABCTB Investigators; HEBON Investigators; BCFR Investigators, Isaacs C98, Jakimovska M99, Jakubowska A24,100, James PA45,101, Janavicius R102, Jankowitz RC103, John EM104, Johnson N70, Joseph V105, Karlan BY106, Khusnutdinova E23,107, Kiiski JI108, Ko YD109, Jones ME110, Konstantopoulou I111, Kristensen VN112,113, Laitman Y72, Lambrechts D114,115, Lazaro C116, Leslie G18, Lester J106, Lesueur F117,118,119, Lindström S120,121, Long J122, Loud JT87, Lubiński J24, Makalic E81, Mannermaa A123,124,125, Manoochehri M91, Margolin S90,126, Maurer T50, Mavroudis D127, McGuffog L18, Meindl A128, Menon U129, Michailidou K18,130, Miller A131, Montagna M132, Moreno F79, Moserle L132, Mulligan AM133,134, Nathanson KL135, Neuhausen SL136, Nevanlinna H108, Nevelsteen I137, Nielsen FC138, Nikitina-Zake L139, Nussbaum RL140, Offit K105,141, Olah E142, Olopade OI143, Olsson H67, Osorio A21,22, Papp J142, Park-Simon TW28, Parsons MT4, Pedersen IS144,145,146, Peixoto A147, Peterlongo P148, Pharoah PDP18,63, Plaseska-Karanfilska D99, Poppe B53, Presneau N64, Radice P149, Rantala J150, Rennert G151, Risch HA152, Saloustros E153, Sanden K154, Sawyer EJ155, Schmidt MK38,156, Schmutzler RK157,158, Sharma P159, Shu XO122, Simard J160, Singer CF14, Soucy P160, Southey MC161,162, Spinelli JJ163,164, Spurdle AB4, Stone J81,165, Swerdlow AJ110,166, Tapper WJ65, Taylor JA167,168, Teixeira MR147,169, Terry MB170, Teulé A171, Thomassen M172, Thöne K50, Thull DL173, Tischkowitz M174,175, Toland AE176, Torres D91,177, Truong T88, Tung N178, Vachon CM179, van Asperen CJ180, van den Ouweland AMW181, van Rensburg EJ182, Vega A183, Viel A184, Wang Q18, Wappenschmidt B157,158, Weitzel JN185, Wendt C126, Winqvist R186,187, Yang XR51, Yannoukakos D111, Ziogas A8, Kraft P188,189, Antoniou AC18, Zheng W122, Easton DF18,63, Milne RL80,81,161, Beesley J4, Chenevix-Trench G4.

Author information

1
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia. Manuel.Ferreira@qimr.edu.au.
2
Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, 37235, USA.
3
Clare Hall, University of Cambridge, Cambridge, CB3 9AL, UK.
4
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
5
Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, 00290, Helsinki, Finland.
6
Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
7
Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
8
Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA, 92617.
9
Department of Pathology, Landspitali University Hospital, 101, Reykjavik, Iceland.
10
BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, 101, Reykjavik, Iceland.
11
Division of Clinical Epidemiology and Aging Research, C070, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
12
Department of Public Health Sciences, and Cancer Research Institute, Queen's University, Kingston, ON, K7L 3N6, Canada.
13
Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
14
Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, 1090, Vienna, Austria.
15
Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), 20133, Milan, Italy.
16
Oncogenetics Group, Vall dHebron Institute of Oncology (VHIO), 8035, Barcelona, Spain.
17
Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), University Hospital, Vall d'Hebron, 08035, Barcelona, Spain.
18
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
19
Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, 91054, Erlangen, Germany.
20
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
21
Centro de Investigación en Red de Enfermedades Raras (CIBERER), 46010, Valencia, Spain.
22
Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), 28029, Madrid, Spain.
23
Institute of Biochemistry and Genetics, Ufa Federal Research Centre of Russian Academy of Sciences, 450054, Ufa, Russia.
24
Department of Genetics and Pathology, Pomeranian Medical University, 71-252, Szczecin, Poland.
25
Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, 00290, Finland.
26
Department of Oncology, Örebro University Hospital, 70185, Örebro, Sweden.
27
Department of Radiation Oncology, Hannover Medical School, 30625, Hannover, Germany.
28
Gynaecology Research Unit, Hannover Medical School, 30625, Hannover, Germany.
29
N.N. Alexandrov Research Institute of Oncology and Medical Radiology, 223040, Minsk, Belarus.
30
Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730, Herlev, Denmark.
31
Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730, Herlev, Denmark.
32
Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
33
Department of Oncology, Lund University and Skåne University Hospital, 222 41, Lund, Sweden.
34
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376, Stuttgart, Germany.
35
University of Tübingen, 72074, Tübingen, Germany.
36
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
37
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120, Heidelberg, Germany.
38
Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 CX, Amsterdam, The Netherlands.
39
Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
40
Molecular Biology of Breast Cancer, University Womens Clinic Heidelberg, University of Heidelberg, 69120, Heidelberg, Germany.
41
Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), 28040, Madrid, Spain.
42
Section of Molecular Genetics, Dept. of Laboratory Medicine, University Hospital of Pisa, 56126, Pisa, Italy.
43
Department of Biology, University of Pisa, 56126, Pisa, Italy.
44
Research Department, Peter MacCallum Cancer Center, Melbourne, VIC, 3000, Australia.
45
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, 3000, Australia.
46
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
47
Department of Gynaecological Oncology, Chris O'Brien Lifehouse and The University of Sydney, Camperdown, NSW, 2050, Australia.
48
Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA, 30303.
49
Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, 36312, Vigo, Spain.
50
Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
51
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, 20850, USA.
52
Departments of Pediatrics and Medicine, Columbia University, New York, NY, 10032, USA.
53
Centre for Medical Genetics, Ghent University, Gent, 9000, Belgium.
54
Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, 2145, Australia.
55
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
56
Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield, S10 2TN, UK.
57
Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, S10 2TN, UK.
58
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65, Stockholm, Sweden.
59
Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.
60
Department of Pathology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
61
Department of Human Genetics, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
62
Clinical and Molecular Genetics Area, University Hospital Vall dHebron, Barcelona, 08035, Spain.
63
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.
64
Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, W1B 2HW, UK.
65
Faculty of Medicine, University of Southampton, Southampton, SO17 1BJ, UK.
66
Department of Oncology, Rigshospitalet, Copenhagen University Hospital, DK-2100, Copenhagen, Denmark.
67
Department of Cancer Epidemiology, Clinical Sciences, Lund University, 222 42, Lund, Sweden.
68
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107, Leipzig, Germany.
69
David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
70
The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, SW7 3RP, UK.
71
Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730, Herlev, Denmark.
72
The Susanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, 52621, Ramat Gan, Israel.
73
Sackler Faculty of Medicine, Tel Aviv University, 69978, Ramat Aviv, Israel.
74
Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, 15706, Santiago de Compostela, Spain.
75
Moores Cancer Center, University of California San Diego, La Jolla, CA, 92037, USA.
76
Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Centre, UCLA, Los Angeles, CA, 90096-6900, USA.
77
Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
78
Division of Genetics and Epidemiology, Institute of Cancer Research, London, SM2 5NG, UK.
79
Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), 28040, Madrid, Spain.
80
Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia.
81
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3010, Australia.
82
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, 3004, Australia.
83
Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, KS, 66160, USA.
84
Department of Medicine, McGill University, Montréal, QC, H4A 3J1, Canada.
85
Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montréal, QC, H4A 3J1, Canada.
86
Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA.
87
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, 20850-9772, USA.
88
Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, 94805, Villejuif, France.
89
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
90
Department of Oncology, Södersjukhuset, 118 83, Stockholm, Sweden.
91
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
92
School of Population and Global Health, The University of Western Australia, Perth, WA, 6009, Australia.
93
Family Cancer Clinic, The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam, 1066 CX, The Netherlands.
94
Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, 3015 CN, The Netherlands.
95
Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL, 60201, USA.
96
The University of Chicago Pritzker School of Medicine, Chicago, IL, 60637, USA.
97
N.N. Petrov Institute of Oncology. St., Petersburg, 197758, Russia.
98
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 20007, USA.
99
Research Centre for Genetic Engineering and Biotechnology 'Georgi D. Efremov', Macedonian Academy of Sciences and Arts, Skopje, 1000, Republic of Macedonia.
100
Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, 71-252, Poland.
101
Parkville Familial Cancer Centre, Peter MacCallum Cancer Center, Melbourne, VIC, 3000, Australia.
102
Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine, Vilnius University Hospital Santariskiu Clinics, Vilnius, 08410, Lithuania.
103
Department of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15232, USA.
104
Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94304, USA.
105
Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
106
David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
107
Department of Genetics and Fundamental Medicine, Bashkir State Medical University, 450076, Ufa, Russia.
108
Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, 00290, Finland.
109
Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, 53177, Germany.
110
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SM2 5NG, UK.
111
Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens, 15310, Greece.
112
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, 0379, Norway.
113
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, 0450, Norway.
114
VIB Center for Cancer Biology, VIB, Leuven, 3001, Belgium.
115
Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, 3000, Belgium.
116
Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Bellvitge Biomedical Research Institute, Catalan Institute of Oncology), CIBERONC, Barcelona, 08908, Spain.
117
Genetic Epidemiology of Cancer team, Inserm U900, Paris, 75005, France.
118
Institut Curie, Paris, 75005, France.
119
Mines ParisTech, Fontainebleau, 77305, France.
120
Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, 98195, USA.
121
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
122
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
123
Translational Cancer Research Area, University of Eastern Finland, Kuopio, 70210, Finland.
124
Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, 70210, Finland.
125
Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, 70210, Finland.
126
Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, 118 83, Sweden.
127
Department of Medical Oncology, University Hospital of Heraklion, Heraklion, 711 10, Greece.
128
Department of Gynecology and Obstetrics, University of Munich, Campus Großhadern, Munich, 81377, Germany.
129
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, University College London, London, WC1V 6LJ, UK.
130
Department of Electron Microscopy/Molecular Pathology and The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology & Genetics, Nicosia, 1683, Cyprus.
131
NRG Oncology, Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA.
132
Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, 35128, Italy.
133
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
134
Laboratory Medicine Program, University Health Network, Toronto, ON, M5G 2C4, Canada.
135
Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, 19066, USA.
136
Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
137
Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, 3000, Belgium.
138
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DK-2100, Denmark.
139
Latvian Biomedical Research and Study Centre, Riga, LV-1067, Latvia.
140
Cancer Genetics and Prevention Program, University of California San Francisco, San Francisco, CA, 94143-1714, USA.
141
Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
142
Department of Molecular Genetics, National Institute of Oncology, Budapest, 1122, Hungary.
143
Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL, 60637, USA.
144
Molecular Diagnostics, Aalborg University Hospital, Aalborg, 9000, Denmark.
145
Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, 9000, Denmark.
146
Department of Clinical Medicine, Aalborg University, Aalborg, 9000, Denmark.
147
Department of Genetics, Portuguese Oncology Institute, Porto, 4220-072, Portugal.
148
Genome Diagnostics Program, IFOM - the FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, 20139, Italy.
149
Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, 20133, Italy.
150
Clinical Genetics, Karolinska Institutet, Stockholm, 171 76, Sweden.
151
Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, 35254, Israel.
152
Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, 06510, USA.
153
Department of Oncology, University Hospital of Larissa, Larissa, 411 10, Greece.
154
City of Hope Clinical Cancer Genetics Community Research Network, Duarte, CA, 91010, USA.
155
Research Oncology, Guy's Hospital, King's College London, London, SE1 9RT, UK.
156
Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam, 1066 CX, The Netherlands.
157
Center for Hereditary Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, 50937, Germany.
158
Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937, Cologne, Germany.
159
Department of Internal Medicine, Division of Oncology, University of Kansas Medical Center, Westwood, KS, 66205, USA.
160
Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval, Research Center, Québec City, QC, G1V 4G2, Canada.
161
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, 3168, Australia.
162
Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC, 3010, Australia.
163
Population Oncology, BC Cancer, Vancouver, BC, V5Z 1G1, Canada.
164
School of Population and Public Health, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
165
The Curtin UWA Centre for Genetic Origins of Health and Disease, Curtin University and University of Western Australia, Perth, WA, 6000, Australia.
166
Division of Breast Cancer Research, The Institute of Cancer Research, London, SW7 3RP, UK.
167
Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, 27709, USA.
168
Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, 27709, USA.
169
Biomedical Sciences Institute (ICBAS), University of Porto, Porto, 4050-013, Portugal.
170
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA.
171
Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute),Catalan Institute of Oncology, CIBERONC, Barcelona, 08908, Spain.
172
Department of Clinical Genetics, Odense University Hospital, Odence C, 5000, Denmark.
173
Department of Medicine, Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
174
Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montréal, QC, H4A 3J1, Canada.
175
Department of Medical Genetics, University of Cambridge, Cambridge, CB2 0QQ, UK.
176
Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, 43210, USA.
177
Institute of Human Genetics, Pontificia Universidad Javeriana, Bogota, 110231, Colombia.
178
Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
179
Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, 55905, USA.
180
Department of Clinical Genetics, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
181
Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, 3015 CN, The Netherlands.
182
Department of Genetics, University of Pretoria, Arcadia, 0007, South Africa.
183
Fundación Pública galega Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela, Spain.
184
Division of Functional onco-genomics and genetics, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, 33081, Italy.
185
Clinical Cancer Genomics, City of Hope, Duarte, CA, 91010, USA.
186
Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, 90570, Finland.
187
Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, 90570, Finland.
188
Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, 02115, MA, USA.
189
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.

Abstract

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.

PMID:
30988301
PMCID:
PMC6465407
DOI:
10.1038/s41467-018-08053-5
[Indexed for MEDLINE]
Free PMC Article

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