supplementary table 1 - media.nature.com · 51saarland cancer registry, saarbrücken, germany....

Supplementary Tables and Supplementary Note

Genome-wide association analysis identifies three new breast cancer susceptibility loci

Maya Ghoussaini1, Olivia Fletcher

2, Kyriaki Michailidou

3, Clare Turnbull

4, Marjanka K Schmidt

5,6, Ed Dicks

1, Joe Dennis

3, Qin Wang

3, Manjeet K

Humphreys3, Craig Luccarini

1, Caroline Baynes

1, Don Conroy

1, Melanie Maranian

1, Shahana Ahmed

1, Kristy Driver

1, Nichola Johnson

2, Nicholas

Orr2, Isabel dos Santos Silva

7, Quinten Waisfisz

8, Hanne Meijers-Heijboer

8, Andre G Uitterlinden

9, Fernando Rivadeneira

9, Netherlands

Collaborative Group on Hereditary Breast and Ovarian Cancer (HEBON)10

, Per Hall11

, Kamila Czene11

, Astrid Irwanto12

, Jianjun Liu13

, Heli

Nevanlinna12

, Kristiina Aittomäki14

, Carl Blomqvist15

, Alfons Meindl16

, Rita KSchmutzler17

, Bertram Müller-Myhsok18

, Peter Lichtner19

, Jenny

Chang-Claude20

, Rebecca Hein20,21

, Stefan Nickels20

, Dieter Flesch-Janys22,23

, Helen Tsimiklis24

, Enes Makalic25

, Daniel Schmidt25

, Minh Bui25

,

John LHopper25

, Carmel Apicella25

, Daniel J Park24

, Melissa Southey24

, David J Hunter26

, Stephen J Chanock27

, Annegien Broeks5, Senno

Verhoef28

, Frans B L Hogervorst29

, Peter A Fasching30

, Michael P Lux30

, Matthias W Beckmann30

, Arif B Ekici31

, Elinor Sawyer32,33

, Ian

Tomlinson34

, Michael Kerin35

, Frederik Marme36,37

, Andreas Schneeweiss36,37

, Christof Sohn36

, Barbara Burwinkel36,38

, Pascal Guénel39,40

, Thérèse

Truong39,40

, Emilie Cordina-Duverger39,40

, Florence Menegaux39,40

, Stig E Bojesen41,42

, Børge G Nordestgaard41,42

, Sune F Nielsen41,42

, Henrik

Flyger43

, Roger L Milne44

, M Rosario Alonso45

, Anna González-Neira45

, Javier Benítez46

, Hoda Anton-Culver47

, Argyrios Ziogas47

, Leslie

Bernstein48

, Christina Clarke Dur49

, Hermann Brenner50

, Heiko Müller50

, Volker Arndt50

, Christa Stegmaier51

, Familial Breast Cancer Study

(FBCS)10

, Christina Justenhoven52,53

, Hiltrud Brauch52,53

, Thomas Brüning54

, The GENICA (Gene Environment Interaction of Breast Cancer in

Germany) Network52–56

, Shan Wang-Gohrke57

, Ursula Eilber20

, Thilo Dörk58

, Peter Schürmann58

, Michael Bremer58

, Peter Hillemanns58

, Natalia V

Bogdanova59

, Natalia N Antonenkova60

, Yuri I Rogov60

, Johann H Karstens59

, Marina Bermisheva61

, Darya Prokofieva61

, Elza Khusnutdinova61

,

Annika Lindblom62

, Sara Margolin63

, Arto Mannermaa64–66

, Vesa Kataja65,67,68

, Veli-Matti Kosma64–66

, Jaana MHartikainen64–66

, Diether

Lambrechts69

, Betul T Yesilyurt69

, Giuseppe Floris70

, Karin Leunen70

, Siranoush Manoukian71

, Bernardo Bonanni72

, Stefano Fortuzzi73

, Paolo

Nature Genetics: doi:10.1038/ng.1049

Peterlongo73,74

, Fergus J Couch75,76

, Xianshu Wang75

, Kristen Stevens76

, Adam Lee77

, Graham G Giles25,78

, Laura Baglietto25,78

, Gianluca Severi25,78

,

Catriona McLean79

, Grethe Grenaker Alnæs80

, Vessela Kristensen80,81

, Anne-Lise Børrensen-Dale80,81

, Esther MJohn49,82

, Alexander Miron83

,

Robert Winqvist84

, Katri Pylkäs84

, Arja Jukkola-Vuorinen85

, Saila Kauppila86

, Irene LAndrulis87,88

, Gord Glendon89

, Anna Marie Mulligan90,91

,

Peter Devilee92,93

, Christie J van Asperen94

, Rob A E M Tollenaar95

, Caroline Seynaeve96

, Jonine D Figueroa27

, Montserrat Garcia-Closas4,97

, Louise

Brinton27

, Jolanta Lissowska98

, Maartje J Hooning99

, Antoinette Hollestelle100

, Rogier A Oldenburg101

, Ans M W van den Ouweland101

, Angela

Cox102

, Malcolm W R Reed103

, Mitul Shah1, Ania Jakubowska

104, Jan Lubinski

104, Katarzyna Jaworska

104, Katarzyna Durda

104, Michael Jones

97,

Minouk Schoemaker97

, Alan Ashworth2, Anthony Swerdlow

97, Jonathan Beesley

105, Xiaoqing Chen

105, kConFab Investigators

10, Australian Ovarian

Cancer Study Group10

, Kenneth R Muir106

, Artitaya Lophatananon106

, Suthee Rattanamongkongul107

, Arkom Chaiwerawattana108

, Daehee Kang109

,

Keun-Young Yoo109

, Dong-Young Noh109

, Chen-Yang Shen110

, Jyh-Cherng Yu111

, Pei-Ei Wu110

, Chia-Ni Hsiung110

, Annie Perkins112

, Ruth

Swann112

, Louiza Velentzis112

, Diana M Eccles113

, Will J Tapper113

, Susan M Gerty113

, Nikki J Graham113

, Bruce A J Ponder114,115

, Georgia

Chenevix-Trench105

, Paul D P Pharoah1,3

, Mark Lathrop116,117

, Alison M Dunning1, Nazneen Rahman

4, Julian Peto

7 & Douglas F Easton

1,3

1Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.

2Breakthrough Breast Cancer Research Centre,

Institute of Cancer Research, London, UK. 3Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge,

Cambridge, UK. 4Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK.

5Department of Experimental Therapy, Netherlands Cancer Institute,

Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. 6Department of Epidemiology, Netherlands Cancer Institute, Antoni van Leeuwenhoek

Hospital, Amsterdam, The Netherlands. 7Non-Communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London,

UK. 8Department of Clinical Genetics, Section Oncogenetics, VU University Medical Center, Amsterdam, The Netherlands.

9Department of Internal Medicine

and Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. 10

A full list of contributing authors is provided in the Supplementary Note. 11

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 12

Department of Obstetrics and Gynecology, University of

Helsinki and Helsinki University Central Hospital, Helsinki, Finland. 13

Human Genetics Division, Genome Institute of Singapore, Singapore. 14

Department of

Clinical Genetics, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. 15

Department of Oncology, University of Helsinki and

Helsinki University Central Hospital, Helsinki, Finland. 16

Clinic of Gynaecology and Obstetrics, Division for Gynaecological Tumor Genetics, Technische

Universität München, Munich, Germany. 17

Department of Obstetrics and Gynaecology, Division of Molecular Gynaeco-Oncology, University of Cologne,

Cologne, Germany. 18

Max Planck Institute of Psychiatry, Munich, Germany. 19

Institute of Human Genetics, Helmholtz Zentrum München, German Research

Center for Environmental Health, Neuherberg, Germany. 20

Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany. 21

PMV


((Primär Medizinische Versorgung) Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne, Cologne,

Germany. 22

Department of Cancer Epidemiology/Clinical Cancer Registry, University Clinic Hamburg-Eppendorf, Hamburg, Germany. 23

Institute for Medical

Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany. 24

Genetic Epidemiology Laboratory, Department of Pathology, The

University of Melbourne, Melbourne, Victoria, Australia. 25

Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, Melbourne School of

Population Health, The University of Melbourne, Melbourne, Victoria, Australia. 26

Program in Molecular and Genetic Epidemiology, Harvard School of Public

Health, Boston, Massachusetts, USA. 27

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA. 28

Department of

Clinical Genetics, Family Cancer Clinic, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. 29

Department of

Molecular Pathology, Family Cancer Clinic, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. 30

Department of

Gynecology and Obstetrics, University Breast Center, University Hospital Erlangen, Erlangen, Germany. 31

Institute of Human Genetics, Friedrich-Alexander

University Erlangen Nuremberg, Erlangen, Germany. 32

Division of Cancer Studies, National Institute for Health Research (NIHR) Comprehensive Biomedical

Research Centre, Guy’s & St. Thomas’ National Health Service (NHS) Foundation Trust, London, UK. 33

Division of Cancer Studies, King’s College London,

London, UK. 34

Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford, UK. 35

Clinical Science

Institute, University Hospital Galway, Galway, Ireland. 36

Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany. 37

National

Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany. 38

Molecular Epidemiology Unit, German Cancer Research Center (DKFZ),

Heidelberg, Germany. 39

Institut National de la Santé et la Recherche Médicale (Inserm), Centre for Research in Epidemiology and Population Health (CESP),

U1018, Environmental Epidemiology of Cancer, Villejuif, France. 40

Université Paris-Sud, UMRS (Unité Mixte de Recherche en Santé) 1018, Villejuif, France. 41

Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark. 42

Department of Clinical Biochemistry,

Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark. 43

Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital,

Copenhagen, Denmark. 44

Genetic & Molecular Epidemiology Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO),

Madrid, Spain. 45

Human Genotyping Unit, Human Cancer Genetics Programme, CNIO, Madrid, Spain. 46

Human Genetics Group, Human Cancer Genetics

Programme, CNIO, Madrid, Spain. 47

Department of Epidemiology, University of California–Irvine, Irvine, California, USA. 48

City of Hope Cancer Centre,

Duarte, California, USA. 49

Cancer Prevention Institute of California, Fremont, California, USA. 50

Division of Clinical Epidemiology and Aging Research,

German Cancer Research Center (DKFZ), Heidelberg, Germany. 51

Saarland Cancer Registry, Saarbrücken, Germany. 52

Dr. Margarete Fischer-Bosch-Institute of

Clinical Pharmacology, Stuttgart, Germany. 53

University of Tübingen, Tübingen, Germany. 54

Institute for Prevention and Occupational Medicine of the German

Social Accident Insurance (IPA), Bochum, Germany. 55

Molecular Genetics of Breast Cancer, DKFZ, Heidelberg, Germany. 56

Department of Internal Medicine,

Evangelische Kliniken Bonn, Johanniter Krankenhaus, Bonn, Germany. 57

Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany. 58

Department of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany. 59

Department of Radiation Oncology, Hannover Medical School,

Hannover, Germany. 60

N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus. 61

Institute of Biochemistry and Genetics, Ufa

Scientific Center of the Russian Academy of Sciences, Ufa, Russia. 62

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 63

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. 64

Department of Pathology and Forensic Medicine, School of Medicine,

Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. 65

Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland. 66

Department

of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland. 67

Department of Oncology, School of Medicine, Institute of Clinical Medicine, University of

Eastern Finland, Kuopio, Finland. 68

Department of Oncology, Kuopio University Hospital, Kuopio, Finland. 69

Vesalius Research Center (VRC), Vlaams Instituut

voor Biotechnologie (VIB), Leuven, Belgium. 70

Multidisciplinary Breast Center, University Hospital Gasthuisberg, Leuven, Belgium. 71

Unit of Medical Genetics,

Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale Tumori (INT),


Milan, Italy. 72

Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy. 73

Istituto FIRC (Fondazione Italiana per la Ricerca

sul Cancero) di Oncologia Molecolare (IFOM), Milan, Italy. 74

Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and

Predictive Medicine, Fondazione IRCCS INT, Milan, Italy. 75

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. 76

Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. 77

Department of Pharmacology, Mayo Clinic, Rochester, Minnesota, USA. 78

Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Victoria, Australia. 79

Department of Anatomical Pathology, Alfred Hospital,

Melbourne, Victoria, Australia. 80

Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway. 81

Institute

for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 82

Division of Epidemiology, Department of Health Research Policy, Stanford

University School of Medicine, Stanford, California, USA. 83

Dana Farber Cancer Center, Boston, Massachusetts, USA. 84

Laboratory of Cancer Genetics,

Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital, Oulu, Finland. 85

Department of Oncology, University of

Oulu, Oulu University Hospital, Oulu, Finland. 86

Department of Pathology, University of Oulu, Oulu University Hospital, Oulu, Finland. 87

Fred A. Litwin Center

for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. 88

Department of Molecular Genetics, University of

Toronto, Toronto, Ontario, Canada. 89

Ontario Cancer Genetics Network, Cancer Care Ontario, Toronto, Ontario, Canada. 90

Department of Laboratory Medicine

and Pathobiology, University of Toronto, Toronto, Ontario, Canada. 91

Department of Laboratory Medicine and the Keenan Research Centre of the Li Ka Shing

Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada. 92

Department of Human Genetics, Leiden University Medical Centre, Leiden, The

Netherlands. 93

Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands. 94

Department of Clinical Genetics, Leiden University

Medical Centre, Leiden, The Netherlands. 95

Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands. 96

Department of Medical

Oncology, Rotterdam Family Cancer Clinic, Erasmus MC–Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. 97

Section of Epidemiology, Institute of

Cancer Research, Sutton, UK. 98

Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,

Warsaw, Poland. 99

Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands. 100

Department of

Medical Oncology, Josephine Nefkens Institute, Erasmus University Medical Center, Rotterdam, The Netherlands. 101

Department of Clinical Genetics, Family

Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands. 102

Institute for Cancer Studies, Department of Oncology, University of

Sheffield, Sheffield, UK. 103

Academic Unit of Surgical Oncology, Department of Oncology, University of Sheffield, Sheffield, UK. 104

Department of Genetics

and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland. 105

Queensland Institute of Medical Research,

Brisbane, Queensland, Australia. 106

Warwick Medical School, Warwick University, Coventry, UK. 107

Department of Preventive Medicine, Srinakharainwirot

University, Ongkharak, Thailand. 108

Department of Academic Support, The National Cancer Institute of Thailand, Ministry of Public Health, Bangkok, Thailand. 109

Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.

110Institute of Biomedical Sciences, Academia Sinica,

Taipei, Taiwan. 111

Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan. 112

Against Breast Cancer Research Group, Department of Molecular and

Applied Biosciences, University of Westminster, London, UK. 113

Faculty of Medicine, University of Southampton, Southampton, UK. 114

Department of

Oncology, University of Cambridge, Cambridge, UK. 115

Cancer Research UK (CRUK) Cambridge Research Institute, Cambridge, UK. 116

Centre National de

Genotypage, Evry, France. 117

Fondation Jean Dausset–Centre d’Etude de Polymorphisme Humaine (CEPH), Paris, France.


Supplementary Tables

Supplementary Table 1. Genotype specific ORs among women of European ancestry, and evidence for heterogeneity in the per-allele OR among

studies, in the BCAC replication.

SNP Chromosome

Position

Het OR

(95%CI)

HomOR

(95%CI)

Heterogeneity P

rs10771399

12p11

280463471

0.85

(0.82-0.88)

0.72

(0.64-0.82)

0.09

rs1292011 12q24

114320905

0.93

(0.90-0.96)

0.85

(0.82-0.89)

0.10

rs2823093 21q21 15442703

0.94

(0.91-0.97)

0.87

(0.83-0.92)

0.002

1 Build 36


Supplementary Table 2. Summary results for all SNPs typed in the BCAC replication stage.

SNP Chr.

Position1 Alleles AF2 UK2 BBCS Other GWAS Combined

P

Per-

allele OR

(95%CI) P Per-allele

OR

(95%CI) P Per-

allele

OR

(95%CI) P

rs3738863 2 30311065 GA 0.732 1.17 (1.09-1.25) 1.6x10-5

1.08 (0.99-1.18) 0.089 1.03 (0.96-1.10) 0.39 0.00059

rs6734368 2 58422570 GA 0.81 1.14 (1.06-1.24) 0.00087 1.06 (0.96-1.17) 0.27 0.93 (0.87-1.00) 0.044 0.47

rs1028246/ rs1403400

$ 2 114319652

TC 0.915 1.22 (1.09-1.36) 0.00044 1.14 (0.98-1.32) 0.090 1.02 (0.92-1.14) 0.64 0.0047

rs13400898 2 154583859 TC 0.062 0.82 (0.72-0.94) 0.0033 0.97 (0.83-1.14) 0.71 1.12 (0.99-1.27) 0.081 0.50

rs10469689 2 163968309 TC 0.058 0.81 (0.71-0.93) 0.0024 0.99 (0.84-1.16) 0.87 0.93 (0.83-1.03) 0.17 0.0083

rs11711782 3 149160340 GA 0.119 0.99 (0.90-1.09) 0.81 0.90 (0.80-1.03) 0.12 0.96 (0.89-1.05) 0.38 0.23

rs9884706 4 32275985 TG 0.844 1.16 (1.07-1.27) 0.00048 1.13 (1.01-1.26) 0.031 1.03 (0.96-1.11) 0.40 0.0019

rs2166278 4 32286120 TC 0.844 1.16 (1.07-1.26) 0.00058 1.13 (1.01-1.26) 0.033 1.03 (0.96-1.11) 0.43 0.0023

rs4403040 4 87257505 TC 0.357 1.11 (1.05-1.19) 0.00088 1.05 (0.97-1.15) 0.23 0.97 (0.91-1.03) 0.29 0.14

rs9761051 4 120233038 CA 0.147 1.16 (1.07-1.27) 0.00056 1.12 (1.01-1.26) 0.041 0.97 (0.90-1.05) 0.50 0.042

rs10940235 5 49672510 TG 0.541 1.04 (0.97-1.10) 0.26 1.12 (1.03-1.21) 0.0060 1.05 (0.99-1.11) 0.080 0.0060

rs820848 5 74000416 GA 0.711 1.13 (1.06-1.21) 0.00034 1.04 (0.93-1.16) 0.50 1.00 (0.93-1.08) 0.92 0.022

rs187727 5 75439941 GA 0.277 1.12 (1.05-1.20) 0.00084 1.09 (1.00-1.19) 0.059 0.99 (0.93-1.06) 0.86 0.029

rs4704018 5 84299468 TC 0.624 1.12 (1.05-1.19) 0.00041 1.08 (0.99-1.17) 0.075 0.98 (0.93-1.04) 0.49 0.044

rs11241138 5 111169939 CA 0.29 0.90 (0.84-0.96) 0.0013 0.90 (0.82-0.99) 0.029 0.99 (0.93-1.05) 0.65 0.0095

rs13160298 5 157728895 GA 0.642 0.98 (0.92-1.04) 0.52 1.06 (0.97-1.15) 0.19 1.06 (1.00-1.13) 0.037 0.15

rs12203592 6 341321 TC 0.772 0.95 (0.88-1.03) 0.20 0.91 (0.74-1.11) 0.35 1.02 (0.92-1.14) 0.66 0.39

rs9467504 6 25522304 GA 0.837 0.84 (0.77-0.91) 2.1x10-5

0.91 (0.81-1.02) 0.12 1.00 (0.93-1.08) 0.95 0.0029

rs12333016 6 107205884 GA 0.9 0.83 (0.75-0.92) 0.00037 1.01 (0.88-1.15) 0.93 1.08 (0.98-1.18) 0.10 0.45

rs9401003 6 117824996 GA 0.781 0.89 (0.83-0.96) 0.0026 1.00 (0.90-1.10) 0.94 0.91 (0.85-0.98) 0.011 0.00065

rs2189630 7 8695731 TG 0.655 0.89 (0.84-0.95) 0.00050 0.92 (0.85-1.00) 0.044 1.04 (0.98-1.11) 0.22 0.085

rs7810604 7 11387506 TC 0.371 0.89 (0.84-0.95) 0.00038 0.87 (0.80-0.94) 0.00064 0.98 (0.93-1.04) 0.60 0.00081

rs1981576 7 82057361 TC 0.087 0.81 (0.72-0.90) 0.00015 0.91 (0.77-1.07) 0.25 1.05 (0.95-1.16) 0.34 0.10

rs1011692 7 121347247 TC 0.123 0.85 (0.78-0.94) 0.00076 0.95 (0.84-1.06) 0.35 1.07 (0.99-1.16) 0.084 0.46

rs2617076 8 4432582 CA 0.4 1.11 (1.04-1.18) 0.0016 0.99 (0.91-1.07) 0.78 0.99 (0.94-1.05) 0.83 0.14

rs4872360 8 22084613 TC 0.259 0.84 (0.78-0.90) 2.1x10-6

0.91 (0.83-1.00) 0.054 0.99 (0.93-1.06) 0.86 0.00099

rs2211914 8 102738843 GA 0.612 0.99 (0.93-1.05) 0.73 0.93 (0.86-1.01) 0.084 0.93 (0.88-0.99) 0.013 0.012

rs4268201+

9 36878148 TG 0.862 0.86 (0.78-0.93) 0.00040 0.96 (0.86-1.08) 0.50 0.99 (0.91-1.07) 0.72 0.020

rs1952461 9 78412404 GA 0.047 1.18 (0.96-1.45) 0.12 1.02 (0.72-1.45) 0.90 0.91 (0.76-1.08) 0.27 0.92

rs1932658 9 86005570 GA 0.727 0.87 (0.81-0.93) 8.3x10-5

0.96 (0.88-1.05) 0.42 0.97 (0.91-1.03) 0.36 0.0029


rs12350727 9 93304437 GA 0.942 0.80 (0.70-0.91) 0.00065 1.05 (0.88-1.26) 0.60 0.96 (0.86-1.08) 0.55 0.039

rs4455975 9 128423020 GA 0.449 1.07 (1.00-1.13) 0.044 1.08 (1.00-1.17) 0.061 1.08 (1.02-1.14) 0.0091 0.00056

rs7074055 10 12665442 GA 0.769 0.90 (0.83-0.96) 0.0028 1.02 (0.91-1.13) 0.75 1.00 (0.93-1.07) 0.89 0.098

rs4746065 10 72183963 CA 0.227 0.88 (0.82-0.95) 0.00074 0.91 (0.82-1.00) 0.039 1.06 (0.99-1.13) 0.083 0.20

rs7116850 11 27602106 GA 0.731 1.15 (1.07-1.23) 8.4x10-5

1.10 (1.00-1.20) 0.042 0.98 (0.92-1.04) 0.47 0.028

rs11604821 11 69061318 GA 0.665 0.87 (0.82-0.93) 4.6x10-5

0.92 (0.85-1.00) 0.054 1.02 (0.96-1.08) 0.47 0.022

rs2284424 12 13880137 GA 0.296 1.12 (1.05-1.20) 0.00083 1.03 (0.95-1.12) 0.50 1.01 (0.95-1.07) 0.84 0.034

rs10771399 12 28046347 GA 0.893 1.27 (1.15-1.41) 3.1x10-6

1.19 (1.05-1.36) 0.0079 1.21 (1.10-1.33) 5.7x10-5

5.7x10-10

rs1975930 12 28053015 TC 0.107 0.79 (0.71-0.87) 2.9x10-6

0.84 (0.74-0.96) 0.0081 0.83 (0.75-0.91) 5.4x10-5

5.3x10-10

rs1292011 12 114320905 GA 0.586 1.14 (1.07-1.21) 5.8x10-5

1.05 (0.97-1.14) 0.23 1.10 (1.04-1.17) 0.00083 9.5x10-7

rs7955262 12 114691345 TC 0.103 1.22 (1.10-1.35) 0.00012 1.06 (0.92-1.22) 0.43 1.02 (0.93-1.12) 0.62 0.0054

rs9586525 13 103922680 TC 0.185 1.16 (1.07-1.25) 0.00026 1.03 (0.92-1.14) 0.63 1.01 (0.94-1.08) 0.86 0.021

rs3784194 14 31993377 TC 0.827 0.94 (0.87-1.02) 0.12 0.95 (0.85-1.05) 0.30 0.96 (0.90-1.04) 0.33 0.066

rs1263441 14 82695911 GA 0.715 1.14 (1.06-1.22) 0.00023 1.03 (0.95-1.13) 0.45 0.99 (0.93-1.05) 0.64 0.067

rs10484150 14 82707696 TC 0.715 1.14 (1.06-1.22) 0.00018 1.04 (0.95-1.13) 0.43 0.98 (0.93-1.05) 0.61 0.063

rs2277509 14 90819348 CA 0.697 1.13 (1.06-1.21) 0.00035 1.00 (0.92-1.09) 0.98 0.99 (0.93-1.05) 0.78 0.085

rs3101649 15 25607717 GA 0.062 1.22 (1.08-1.38) 0.0020 1.08 (0.85-1.36) 0.54 1.05 (0.93-1.18) 0.45 0.010

rs12443310 15 52387367 TC 0.911 0.82 (0.74-0.91) 0.00024 0.88 (0.76-1.01) 0.075 0.95 (0.86-1.06) 0.37 0.0013

rs1873062 17 3292880 TC 0.19 0.86 (0.80-0.93) 0.00022 0.91 (0.82-1.00) 0.051 0.96 (0.90-1.03) 0.29 0.00095

rs1990236 17 11806187 GA 0.189 1.16 (1.07-1.25) 0.00025 1.12 (1.01-1.24) 0.032 1.10 (1.03-1.18) 0.0082 6.6x10-6

rs231020 17 15103114 TC 0.52 0.88 (0.83-0.93) 3.7x10-5

0.95 (0.88-1.03) 0.18 1.05 (0.99-1.11) 0.088 0.14

rs1526123 17 41139123 TC 0.463 0.90 (0.84-0.95) 0.00047 0.89 (0.82-0.97) 0.0063 0.95 (0.90-1.01) 0.11 8.8x10-5

rs7206949 17 41602794 CA 0.396 1.14 (1.07-1.21) 6.4x10-5

1.30 (1.13-1.49) 0.00021 0.98 (0.92-1.05) 0.55 0.0078

rs2668632* 17 41675143 AG 0.758 1.13 (1.05-1.22) 0.0011 0.0011

rs2532348* 17 41696030 GA 0.762 1.13 (1.05-1.22) 0.0011 0.0011

rs199523* 17 42203685 CA 0.743 1.15 (1.07-1.24) .00011 .00011

rs4968451 17 57282089 CA 0.842 0.84 (0.77-0.91) 1.9x10-5

0.90 (0.81-1.00) 0.055 0.99 (0.92-1.06) 0.72 0.0022

rs4522464 17 57553912 TG 0.135 1.20 (1.10-1.31) 5.0x10-5

1.14 (1.00-1.30) 0.047 0.99 (0.92-1.08) 0.87 0.0070

rs2233768 17 64656171 TC 0.949 0.81 (0.71-0.93) 0.0035 0.94 (0.78-1.13) 0.52 1.05 (0.93-1.18) 0.46 0.23

rs12606686 18 9032622 GA 0.082 1.18 (1.06-1.32) 0.0036 0.91 (0.77-1.07) 0.23 1.03 (0.92-1.15) 0.63 0.096

rs1175745 18 22841047 CA 0.601 1.07 (1.01-1.14) 0.028 1.14 (1.05-1.23) 0.0018 1.05 (1.00-1.12) 0.066 0.00055

rs3886058 18 33702576 GA 0.44 0.95 (0.89-1.01) 0.097 0.92 (0.85-1.00) 0.057 0.99 (0.93-1.05) 0.68 0.084

rs8098165 18 65319547 TC 0.685 1.03 (0.96-1.10) 0.41 1.01 (0.93-1.10) 0.73 1.09 (1.02-1.15) 0.0057 0.011

rs4536550 18 69099471 GA 0.303 1.01 (0.94-1.08) 0.82 1.12 (1.02-1.21) 0.013 0.99 (0.93-1.05) 0.70 0.54

rs2163823 19 43684018 GA 0.247 0.90 (0.83-0.96) 0.0027 1.06 (0.96-1.16) 0.23 0.93 (0.87-0.99) 0.020 0.0038

rs6027564 20 58389556 GA 0.901 1.15 (1.03-1.27) 0.0095 0.99 (0.86-1.15) 0.94 1.03 (0.94-1.13) 0.55 0.11

rs2823093 21 15442703 GA 0.262 0.96 (0.89-1.03) 0.21 0.83 (0.76-0.92) 0.00013 0.91 (0.85-0.97) 0.0032 9.5x10-5

rs2837766 21 40950152 TC 0.615 1.12 (1.05-1.19) 0.00036 1.12 (1.03-1.21) 0.0068 1.00 (0.94-1.06) 0.94 0.0067

rs7285871 22 16242268 TC 0.437 0.89 (0.84-0.95) 0.00042 0.90 (0.83-0.98) 0.012 1.00 (0.94-1.06) 0.96 0.0055

rs1541326 22 18034452 GA 0.292 1.16 (1.08-1.24) 1.4x10-5

1.01 (0.92-1.10) 0.89 0.99 (0.93-1.06) 0.72 0.024

rs547043 X 150007811 GA 0.448 1.18 (1.10-1.28) 1.3x10-5

1.20 (1.09-1.31) 8.6x10-5

1.03 (0.97-1.10) 0.31 7.9x10-5


(b) GWAS+BCAC replication

rs5970292 X 151231436 GA 0.644 0.85 (0.79-0.92) 2.5x10-5

0.91 (0.83-1.00) 0.060 0.93 (0.87-0.99) 0.020 2.1x10-5

rs6627588 X 151264915 CA 0.274 1.20 (1.11-1.31) 7.5x10-6

1.18 (1.05-1.32) 0.0065 1.12 (1.05-1.20) 0.0014 1.1x10-7

SNP Chr.

Position1 Alleles AF2 All GWAS BCAC Combined

P

Per-

allele

OR

(95%CI) P Per-

allele

OR

(95%CI) P

rs3738863 2 30311065 GA 0.732 1.08 (1.03-1.13) 0.00059 1.00 (0.98-1.02) 0.87 0.15

rs6734368 2 58422570 GA 0.81 1.02 (0.97-1.07) 0.47 1.02 (0.99-1.05) 0.12 0.084

rs1028246/ rs1403400

$ 2 114319652

TC 0.915 1.11 (1.03-1.19) 0.0047 1.04 (0.98-1.11) 0.20 0.0043

rs13400898 2 154583859 TC 0.062 0.97 (0.89-1.06) 0.50 0.98 (0.91-1.07) 0.68 0.45

rs10469689 2 163968309 TC 0.058 0.90 (0.83-0.97) 0.0083 1.02 (0.98-1.06) 0.30 0.77

rs11711782 3 149160340 GA 0.119 0.96 (0.91-1.02) 0.23 1.00 (0.97-1.03) 0.76 0.41

rs9884706 4 32275985 TG 0.844 1.09 (1.03-1.15) 0.0019 1.01 (0.96-1.06) 0.76 0.018

rs2166278 4 32286120 TC 0.844 1.09 (1.03-1.14) 0.0023 1.01 (0.96-1.06) 0.82 0.024

rs4403040 4 87257505 TC 0.357 1.03 (0.99-1.07) 0.14 1.03 (1.01-1.05) 0.0067 0.0020

rs9761051 4 120233038 CA 0.147 1.06 (1.00-1.12) 0.042 0.99 (0.94-1.04) 0.63 0.29

rs10940235 5 49672510 TG 0.541 1.06 (1.02-1.10) 0.0060 1.03 (1.01-1.05) 0.0016 6.0x10-5

rs820848 5 74000416 GA 0.711 1.06 (1.01-1.11) 0.022 1.00 (0.98-1.02) 0.92 0.30

rs187727 5 75439941 GA 0.277 1.05 (1.01-1.10) 0.029 1.01 (0.97-1.05) 0.68 0.069

rs4704018 5 84299468 TC 0.624 1.04 (1.00-1.08) 0.044 1.00 (0.97-1.04) 0.85 0.13

rs11241138 5 111169939 CA 0.29 0.94 (0.91-0.99) 0.0095 0.99 (0.97-1.01) 0.39 0.051

rs13160298 5 157728895 GA 0.642 1.03 (0.99-1.07) 0.15 0.98 (0.93-1.02) 0.21 0.63

rs12203592 6 341321 TC 0.772 0.97 (0.91-1.04) 0.39 1.01 (0.97-1.04) 0.73 0.90

rs9467504 6 25522304 GA 0.837 0.92 (0.87-0.97) 0.0029 1.01 (0.96-1.06) 0.71 0.082

rs12333016 6 107205884 GA 0.9 0.98 (0.91-1.04) 0.45 1.02 (0.96-1.09) 0.43 0.96

rs9401003 6 117824996 GA 0.781 0.92 (0.88-0.97) 0.00065 1.00 (0.96-1.05) 0.91 0.022

rs2189630 7 8695731 TG 0.655 0.96 (0.92-1.01) 0.085 1.01 (0.98-1.03) 0.60 0.75

rs7810604 7 11387506 TC 0.371 0.93 (0.90-0.97) 0.00081 1.00 (0.97-1.02) 0.65 0.052

rs1981576 7 82057361 TC 0.087 0.94 (0.88-1.01) 0.10 1.00 (0.94-1.06) 0.90 0.24

rs1011692 7 121347247 TC 0.123 0.98 (0.93-1.04) 0.46 0.99 (0.90-1.08) 0.81 0.45

rs2617076 8 4432582 CA 0.4 1.03 (0.99-1.07) 0.14 1.00 (0.96-1.04) 1.0 0.31

rs4872360 8 22084613 TC 0.259 0.93 (0.89-0.97) 0.00099 0.99 (0.97-1.02) 0.63 0.053


rs2211914 8 102738843 GA 0.612 0.95 (0.91-0.99) 0.012 1.00 (0.96-1.04) 0.88 0.066

rs4268201 9 36878148 TG 0.862 0.94 (0.89-0.99) 0.020 0.99 (0.96-1.02) 0.54 0.098

rs1952461 9 78412404 GA 0.047 0.99 (0.87-1.13) 0.92 0.98 (0.91-1.05) 0.51 0.53

rs1932658 9 86005570 GA 0.727 0.94 (0.90-0.98) 0.0029 1.02 (0.99-1.05) 0.12 0.79

rs12350727 9 93304437 GA 0.942 0.92 (0.84-1.00) 0.039 1.00 (0.93-1.08) 0.96 0.15

rs4455975 9 128423020 GA 0.449 1.07 (1.03-1.11) 0.00056 1.02 (0.98-1.06) 0.30 0.0017

rs7074055 10 12665442 GA 0.769 0.96 (0.92-1.01) 0.098 0.99 (0.95-1.04) 0.68 0.15

rs4746065 10 72183963 CA 0.227 0.97 (0.93-1.02) 0.20 1.01 (0.99-1.04) 0.24 0.66

rs7116850 11 27602106 GA 0.731 1.05 (1.01-1.10) 0.028 0.97 (0.93-1.01) 0.11 0.73

rs11604821 11 69061318 GA 0.665 0.95 (0.91-0.99) 0.022 0.97 (0.93-1.01) 0.093 0.0053

rs2284424 12 13880137 GA 0.296 1.05 (1.00-1.09) 0.034 1.03 (0.99-1.07) 0.17 0.014

rs10771399 12 28046347 GA 0.893 1.22 (1.15-1.31) 5.7x10-10

1.18 (1.14-1.21) 3.3x10-27

2.7x10-35

rs1975930 12 28053015 TC 0.107 0.82 (0.77-0.87) 5.3x10-10

0.83 (0.79-0.87) 1.4x10-15

5.7x10-24

rs1292011 12 114320905 GA 0.586 1.10 (1.06-1.15) 9.5x10-7

1.08 (1.06-1.10) 6.2x10-14

4.8x10-19

rs7955262 12 114691345 TC 0.103 1.10 (1.03-1.17) 0.0054 1.04 (0.98-1.10) 0.18 0.0042

rs9586525 13 103922680 TC 0.185 1.06 (1.01-1.12) 0.021 1.03 (0.98-1.08) 0.27 0.016

rs3784194 14 31993377 TC 0.827 0.95 (0.91-1.00) 0.066 1.03 (1.00-1.05) 0.034 0.30

rs1263441 14 82695911 GA 0.715 1.04 (1.00-1.09) 0.067 1.06 (0.99-1.14) 0.089 0.015

rs10484150 14 82707696 TC 0.715 1.04 (1.00-1.09) 0.063 1.05 (0.92-1.21) 0.48 0.047

rs2277509 14 90819348 CA 0.697 1.04 (0.99-1.08) 0.085 1.04 (1.00-1.08) 0.060 0.011

rs3101649 15 25607717 GA 0.062 1.12 (1.03-1.22) 0.010 1.00 (0.96-1.04) 0.98 0.28

rs12443310 15 52387367 TC 0.911 0.89 (0.83-0.96) 0.0013 1.04 (1.00-1.08) 0.043 0.85

rs1873062 17 3292880 TC 0.19 0.92 (0.88-0.97) 0.00095 0.97 (0.93-1.02) 0.19 0.0013

rs1990236 17 11806187 GA 0.189 1.12 (1.07-1.18) 6.6x10-6

1.02 (0.99-1.05) 0.12 0.00052

rs231020 17 15103114 TC 0.52 0.97 (0.93-1.01) 0.14 0.99 (0.96-1.03) 0.77 0.22

rs1526123 17 41139123 TC 0.463 0.92 (0.89-0.96) 8.8x10-5

0.99 (0.96-1.03) 0.76 0.0038

rs7206949 17 41602794 CA 0.396 1.06 (1.02-1.11) 0.0078 1.01 (0.98-1.05) 0.48 0.024

rs2668632* 17 41675143 AG 0.758 1.13 (1.05-1.22) 0.0011 1.05 (1.01-1.10) 0.028 0.00031

rs2532348* 17 41696030 GA 0.762 1.13 (1.05-1.22) 0.0011 1.08 (1.04-1.12) 7.8x10-5

5.8x10-7

rs199523* 17 42203685 CA 0.743 1.15 (1.07-1.24) .00011 1.12 (1.03-1.21) 0.0063 2.6x10-6

rs4968451 17 57282089 CA 0.842 0.92 (0.88-0.97) 0.0022 0.98 (0.93-1.03) 0.34 0.0048

rs4522464 17 57553912 TG 0.135 1.08 (1.02-1.15) 0.0070 1.02 (0.97-1.08) 0.38 0.014

rs2233768 17 64656171 TC 0.949 0.95 (0.87-1.03) 0.23 1.05 (0.96-1.14) 0.29 0.93

rs12606686 18 9032622 GA 0.082 1.07 (0.99-1.15) 0.096 0.98 (0.94-1.02) 0.39 0.95

rs1175745 18 22841047 CA 0.601 1.07 (1.03-1.12) 0.00055 1.00 (0.97-1.04) 0.80 0.010

rs3886058 18 33702576 GA 0.44 0.97 (0.93-1.00) 0.084 0.99 (0.97-1.01) 0.60 0.20

rs8098165 18 65319547 TC 0.685 1.05 (1.01-1.10) 0.011 0.98 (0.95-1.00) 0.048 0.64

rs4536550 18 69099471 GA 0.303 1.01 (0.97-1.06) 0.54 1.01 (0.97-1.05) 0.74 0.51

rs2163823 19 43684018 GA 0.247 0.94 (0.89-0.98) 0.0038 1.01 (0.96-1.05) 0.82 0.054

rs6027564 20 58389556 GA 0.901 1.06 (0.99-1.13) 0.11 1.08 (1.02-1.15) 0.010 0.0029

rs2823093 21 15442703 GA 0.262 0.92 (0.88-0.96) 9.5x10-5

0.94 (0.92-0.96) 1.7x10-9

1.1x10-12


1 Build 36

2 Frequency of the 2

nd listed allele

* SNPs not on HapMap 2, GWAS results from genotyped data (UK2 only)

+ SNP not on HapMap 2, GWAS results imputed from HapMap3

$ GWAS results for SNP rs1028246, surrogate rs1403400 typed in the BCAC replication

rs2837766 21 40950152 TC 0.615 1.06 (1.02-1.10) 0.0067 0.97 (0.94-1.01) 0.18 0.38

rs7285871 22 16242268 TC 0.437 0.94 (0.91-0.98) 0.0055 0.98 (0.95-1.02) 0.40 0.013

rs1541326 22 18034452 GA 0.292 1.05 (1.01-1.10) 0.024 0.97 (0.95-0.99) 0.012 0.22

rs547043 X 150007811 GA 0.448 1.10 (1.05-1.15) 7.9x10-5

1.02 (0.98-1.05) 0.40 0.0018

rs5970292 X 151231436 GA 0.644 0.90 (0.86-0.95) 2.1x10-5

1.02 (1.00-1.04) 0.13 0.71

rs6627588 X 151264915 CA 0.274 1.15 (1.09-1.21) 1.1x10-7

1.03 (0.99-1.07) 0.20 2.0x10-5


Supplementary Table 3. Estimated per-allele ORs for Asian women from BCAC.

SNP Chromosome

Position

MAF Per-allele

OR

(95%CI)

P P for

difference

with OR for

European

women

rs10771399

12p11

28046347

0.11 0.85

(0.77-0.94)

0.002

0.93

rs1292011 12q24

114320905

0.41 0.95

(0.85-1.07)

0.43

0.59

rs2823093 21q21 15442703

0.26 1.14

(0.93-1.40)

0.20

0.058


Supplementary Table 4. Estimated per-allele ORs by ER-status, DCIS vs invasive disease, and age at diagnosis from the BCAC replication.

(a) Estimated ORs by ER-status

SNP Chromosome

Position

No.

Controls

No.

ER+ cases

ER+

Per-allele

OR

(95%CI)

P No.

ER- cases

ER-

Per-allele

OR

(95%CI)

P P-diff

rs10771399

12p11

28046347

48,368 24,775 0.87

(0.84-0.90)

4.5x10-14

7,122 0.85

(0.80-0.90)

6.3x10-8

.46

rs1292011 12q24

114320905

40,739 18,394 0.90

(0.87-0.92)

2.0x10-15

5,167 0.99

(0.94-1.03)

.55 .0001

rs2823093 21q21 15442703

46,063 21,409 0.93

(0.90-0.95)

4.6x10-8

6,093 0.99 (0.95-

1.04)

.72 .02

(b) Estimated ORs for DCIS.

SNP No. controls No. DCIS

cases

Chromosome

Position

Per-allele

OR

(95%CI)

P

(vs.controls)

P

(vs.invasive

disease)

rs10771399

33,767 2,148 12p11

28046347

0.89

(0.80-0.99)

.026

0.50

rs1292011 28,588 1,566 12q24

114320905

0.92

(0.86-1.00)

.043

0.80

rs2823093 31,543 1,881 21q21 15442703

0.94

(0.87-1.01)

.11

0.39


(c) Estimated per-allele ORs by age-group.

SNP Age group P-trend

<40 40-49 50-59 60+

rs10771399 0.83

(0.75-0.92)

0.81

(0.75-0.87)

0.86

(0.81-0.91)

0.88

(0.84-0.93)

.31

rs1292011 0.96

(0.90-1.04)

0.91

(0.87-0.96)

0.93

(0.89-0.96)

0.92

(0.89-0.95)

.25

rs2823093 0.96

(0.90-1.04)

0.94

(0.90-0.99)

0.92

(0.89-0.96)

0.94

(0.91-0.97)

.58


Supplementary Table 5. Estimated per-allele ORs among studies in which cases were selected or unselected for family history/bilaterality from the

BCAC replication.

SNP Unselected studies Selected studies P diff

Per-allele

OR

(95%CI)

P Per-allele OR

(95%CI)

P

rs10771399

0.86

(0.83-0.89)

8.6x10-21

0.79

(0.73-0.85)

4.4x10-10

.027

rs1292011 0.92

(0.90-0.95)

4.1x10-21

0.92

(0.87-0.97)

.0013 .80

rs2823093 0.94

(0.92-0.96)

3.9x10-8

0.91

(0.86-0.97)

.0017 .31


Supplementary Table 6. Genome-wide association studies contributing to the current analysis.

Study Country Case

ascertainment

Control

ascertainment

Genotyping

platform

Cases1

Controls1

Reference

ABCFS/kConFab Australia Recruitment

through cancer

registries in

Victoria and

New South

Wales

Recruitment

from the

electoral rolls

in Melbourne

and Sydney

matched to

cases by age

in-5 year

categories

Illumina 610k 282 285 1

BBCS UK Recruitment

through cancer

registries in UK,

predominantly

bilateral cases

WTCCC2:

1958 Birth

Cohort + UK

National Blood

Service

Illumina 370k

(cases)

Illumina 1.2M

(controls)

1609 5190 2

CGEMS USA Postmenopausal

cases from

Nurses Health

Study

Individually

matched

controls from

Nurses Health

Study

Illumina 550k 1127 1130 3

GC-HBOC Germany BRCA1/2

mutation

negative cases

from University

Clinics in

Cologne and

Munich

KORA

(Cooperative

Health

Research in the

Region

Augsburg)

Affymetrix 5.0k

(cases)

Affymetrix 6.0k

(controls)

634 477 4

MARIE Germany Random sample

of cases from the

MARIE study,

but restricted to

KORA

(Cooperative

Health

Research in the

Illumina 370k

(cases)

Illumina 550k

(controls)

708 470 5


ductal and

lobular

carcinomas and

oversampled for

lobular (about

2:1)

Region

Augsburg)

HEBCS Finland Unselected cases

plus additional

familial cases

from Helsinki

University

Central Hospital

Healthy

Population

Controls from

Finnish

Genome

Centre

(NordicDB)

Illumina 550k +

610k (cases)

Illumina 370k

(controls)

810 1012 6, 7

SASBAC Sweden Population-

based case

control study of

postmenopausal

women

Population-

based controls

frequency

matched by

age to cases

Illumina

317k+240k

(cases)

Illumina 550k

(controls)

790 756 7

UK2 UK UK cancer

genetics clinics

+ oncology

clinicas

WTCCC2:

1958 Birth

Cohort + UK

National Blood

Service

Illumina 670k

(cases)

Illumina 1.2M

(controls)

3628 5190 8

DFBBCS Netherlands BRCA1/2

mutation

negative familial

bilateral breast

cancer patients

selected from

five clinical

genetics centers;

Erasmus

University

Medical

Controls were

from the

Rotterdam

study, and are

55 years or

older at the

time of

inclusion. For

this study

females were

selected and

Illumina 610k

(cases)

Illumina 550k

(controls)

464 3255 9


Center/Daniel

den Hoed, The

Netherlands

Cancer Institute,

Leiden

University

Medical Center,

University

Medical Center

Utrecht, and VU

University

Medical Center.

breast cancer

cases were

excluded.

1Final numbers used in the analysis, after QC.


Supplementary Table 7. Participating studies in the BCAC replication phase.

Study

Acronym

Study Name

[Reference]

Country

Recruitment base

Cases Controls

STUDIES OF WHITE EUROPEAN WOMEN

ABCFR Australian Breast

Cancer Family Study 1

Australia

Cancer registries in Victoria and New South Wales

(1992-1999): all cases from Melbourne and Sydney

diagnosed before age 40 plus a random sample of

those diagnosed at ages 40-59

Identified between 1992-1999 from the electoral

rolls in Melbourne and Sydney (enrolling to vote is

compulsory); frequency matched to cases by age in-

5 year categories

ABCS Amsterdam Breast

Cancer Study 10

Netherlands

(ABCS-F) All non-BRCA1/2 breast cancer cases

from the family cancer clinic of the NKI-AVL

tested in the period 1995-2009; all ages and

diagnosed with breast cancer in 1965-2008..

Randomly selected women from population-based

prospective cohort studies, aged <50 at baseline

(1987-1991 and 1993-1997) and from the same

areas as cases.

BBCC

Bavarian Breast

Cancer Cases and

Controls 11

Germany

Consecutive, unselected cases with invasive breast

cancer recruited at the University Breast Centre,

Franconia in Northern Bavaria from 2002-2006

Healthy women aged 55 or older with no diagnosis

of cancer. Invited by a newspaper advertisement in

Northern Bavaria between 2002-2006

BBCS British Breast Cancer

Study 2

U.K.

(i) English & Scottish Cancer Registries: all breast

cancer cases who developed a first primary before

age 66 in 1971 or later and who subsequently

developed a second primary cancer

(ii) Breast Cancer Clinics: all breast cancer cases

who developed a first primary before age 71 in 1967

or later and who either subsequently developed a

second primary or had at least two affected female

first-degree relatives.

All recruited from 2001-2008.

A friend, sister-in-law, daughter-in-law or other

non-blood relative of cases, recruited from 2001-

2008

BIGGS

Breast Cancer in

Galway Genetic Study 12

Ireland

Unselected cases recruited from University College

Hospital Galway and surrounding hospitals in the

West of Ireland since 2001

Women > 60 years with no personal history of any

cancer and no family history of breast or ovarian

cancer identified from retirement groups in the West

of Ireland between 2001-2008.

BSUCH

Breast Cancer Study of

the University Clinic

Heidelberg 13

Germany All cases diagnosed with breast cancer in 2007-2009

at the University Women`s Clinic Heidelberg

Female blood donors recruited in 2007- 2009 at the

Institute of Transfusion Medicine & Immunology,

Mannheim.


CECILE CECILE Breast cancer

study 14

France

All cases diagnosed with breast cancer in 2005-2007

among women <75 years of age residing in the

départements of Ille-et-Vilaine and Côte d'Or .

Cases were recruited from the main cancer

treatment center (Centre Eugène-Marquis in Rennes

and Centre Georges-François-Leclerc in Dijon) and

from other private or public hospitals in each area.

General population control women residing in the

same areas as the cases (Ille-et-Vilaine and Côte

d’Or). Controls were frequency-matched to the

cases by 5-year age groups. They were recruited in

2005-2007 using a random digit dialing procedure

and quotas by socioeconomic status to reflect the

distribution by SES of the population in each area.

CGPS Copenhagen General

Population Study 15

Denmark

Consecutive, incident cases from one hospital with

centralized care for a population of 400,000 women

in Copenhagen (2001-present)

Women with no history of breast cancer residing in

the same region as cases identified from the

Copenhagen General Population Study (2003-2007)

CNIO-BCS

Spanish National

Cancer Centre Breast

Cancer Study 16

Spain

(i) consecutive breast cancer patients from three

public hospitals, two in Madrid and one in Oviedo;

(ii) cases with at least one affected first degree

relative recruited through the CNIO family cancer

clinic in Madrid (2000-2005)

Women attending the Menopause Research Centre,

Madrid and female members of the College of

Lawyers attending a free, targeted medical check-up

in Madrid, all free of breast cancer and all in Madrid

between 2000-2005

CTS California Teachers

Study 17

USA

Nested case-control study conducted within a cohort

of California teachers (113,590) who were under

age 80 years at baseline, had no prior history of

invasive or in situ breast cancer. Cases are

women newly diagnosed with a histologically

confirmed invasive primary adenocarcinoma of the

breast at age 80 years or younger from 1998 to

2008.

Controls are a probability sample of at-risk cohort

members, frequency matched to cases on age at

baseline (5-year age

groups), self-reported race/ethnicity (white, African

American, Latina,Asian, other), and broad

geographic region within California

Controls were selected without replacement, using

an assigned reference

date.

ESTHER ESTHER Breast

Cancer Study 18

Germany

Breast cancer cases in all hospitals in the state of

Saarland, from 2001-2003 (ESTHER) and 1996-

1998 (VERDI)

Random sample of women a routine health check-

up in Saarland, in 2000-2002; frequency matched to

cases by age in-5 year categories

GC-HBOC German Familial

Breast Cancer Study 4

Germany

Index patients from German breast cancer families;

BRCA1/2 mutation free, collected 1996-2007 via

Institute of Human Genetics, University Heidelberg

Department of Gynaecology & Obstetrics, Cologne

& Department of Gynaecology and Obstetrics at the

Ludwig-Maximilians-University, Munich

Female blood donors recruited in 2004 & 2007 at

the Institute of Transfusion Medicine &

Immunology, Mannheim.

GENICA Gene Environment Germany Incident breast cancer cases enrolled at hospitals Random address sample selected in 2001-2004 from


Interaction & Breast

Cancer in Germany 19,

20

in the Greater Bonn area between 2000-2004 31 population registries in the greater Bonn area;

frequency matched to cases on year of birth in 5-

year categories

GESBC

Genetic Epidemiology

Study of Breast Cancer

by Age 50 21

Germany

All incident cases diagnosed <50 years of age in

1992-5 in two regions: Rhein-Neckar-Odenwald and

Freiburg, by surveying the 38 clinics serving these

regions

Selected from random lists of residents of the study

regions supplied by population registries; two

controls were selected for each case, matched by

age and study region. Recruitment was carried out

1992-1998.

HABCS Hannover Breast

Cancer Study 22

Germany

Cases who received radiotherapy for breast cancer

at Hannover Medical School 1995-2003

Female blood bank donors at Hannover Medical

School, collected in 2005

HEBCS Helsinki Breast Cancer

Study Finland

(1) Consecutive cases (883) from the Department

of Oncology, Helsinki University Central Hospital

1997-8 and 2000, (2) Consecutive cases (986) from

the Department of Surgery, Helsinki University

Central Hospital 2001 – 2004, (3) Familial breast

cancer patients (536) from the Helsinki University

Central Hospital, Departments of Oncology and

Clinical Genetics (1995-)

Healthy females from the same geographical region

in Southern Finland in 2003.

HMBCS Hannover-Minsk


Belarus

Cases from the Byelorussian Institute for Oncology

and Medical Radiology Aleksandrov N.N. in Minsk

or at one of 5 regional oncology centers in Gomel,

Mogilev, Grodno, Brest or Vitebsk (2002-2008)

Women attending general medical examination at

gynecology clinics in Gomel, Mogilev, Grodno,

Brest or Vitebsk; women attending the Institute for

Inherited Diseases in Minsk; female blood donors in

Minsk; healthy relatives of cases (2002-2008)


HUBCS Hannover-Ufa Breast

Cancer Study 23

Russia

Consecutive cancer patients diagnosed at two

participating oncological centers in Bashkorstostan

and Siberia between 2000-2008

Healthy volunteers selected from poulation studies

in the same geographical regions during 2002-2008.

KARBAC Karolinska Breast

Cancer Study Sweden

1. Familial cases from Department of Clinical

Genetics, Karolinska University Hospital ,

Stockholm. 2. Consecutive cases from Department

of Oncology, Huddinge & Söder Hospital,

Stockholm 1998-2000

Blood donors of mixed gender from same

geographical region. Excess material was received

from all blood donors over a 3 month period in 2004

(approximately 3000) and DNA was extracted from

a random sample of 1500

KBCP Kuopio Breast Cancer

Project 24

Finland

Women seen at Kuopio University Hospital

between 1990-1995 because of a breast lump,

mammographic abnormality, or other breast

symptom and who were found to have breast cancer

Selected from the National Population Register

between 1990-1995; age and long-term area-of-

residence matched to cases

kConFab/

AOCS

Kathleen Cuningham

Foundation

Consortium for

Research into Familial

Breast Cancer /

Australian Ovarian

Cancer Study 25

Australia

Index (youngest affected) cases from BRCA1- and

BRCA2-mutation-negative multiple-case breast and

breast-ovarian families recruited though family

cancer clinics from across Australia and New

Zealand from 1998-present

Identified from the electoral rolls from across

Australia as part of the Australian Ovarian Cancer

Study in 2002-2006

LMBC

Leuven

Multidisciplinary

Breast Centre 26

Belgium

All patients diagnosed with breast cancer and seen

in the Multidisciplinary Breast Center in Leuven

(Gashuisberg) since June 2007 plus retrospective

collection of cases diagnosed since 2000

Blood donors at Gasthuisberg Hospital (200-2008)

MARIE

Mammary Carcinoma

Risk Factor

Investigation 5

Germany

Incident cases diagnosed from 2001-2005 in the

study region Hamburg in Northern Germany, and

from 2002-2005 in the study region Rhein-Neckar-

Karlsruhe in Southern Germany.

2 controls per case were randomly drawn from

population registries and frequency matched by

birth year and study region to the case. Controls

were recruited from 2002 to 2006.

MBCSG Milan Breast Cancer

Study Group 27

Italy

Familial and/or early onset breast cancer patients

(aged 22-87) negative for mutations in BRCA1 and

BRCA2, ascertained at two large cancer centers in

Milan from 2000-present

Female blood donors recruited at two centres in

Milan from 2004-present and 2007-present

MCBCS Mayo Clinic Breast

Cancer Study 28

U.S.A.

Incident cases residing in 6 states (MN, WI, IA, IL,

ND, SD) seen at the Mayo Clinic in Rochester, MN

from 2002-2010

Women presenting for general medical examination

at the Mayo Clinic from 2002-2010; frequency

matched to cases on age, ethnicity and county/state


MCCS

Melbourne

Collaborative Cohort

Study 29

Australia

Incident cases from the cohort of 24,469 women,

diagnosed during the follow-up from baseline

(1990-1994) to 2008

Random sample of the initial cohort

NBCS Norwegian Breast

Cancer Study 30

Norway

Incidence cases from three different hospitals:

Ullevål Univ. Hospital 1990-94, Norwegian Radium

Hospital 1975-1986 and 1995-1998, Haukeland

Univ. Hospital 1992-2001

Women residing in Tromsø and Bergen who

attended the Norwegian Breast Cancer Screening

Program.

NC-BCFR

Northern California

Breast Cancer Family

Registry 31

U.S.A.

Incident cases aged <65 years identified through the

SEER cancer registry of the Greater San Francisco

Bay Area from 1995-2003. All cases likely at

increased genetic risk were selected; 2.5% of white

cases not meeting these criteria were randomly

sampled

Identified through random digit dialling conducted

in the same geographic region from 1999-2000;

frequency matched to cases diagnosed from 1995-

1998 on 5-year age group and race/ethnicity

OBCS Oulu Breast Cancer

Study 32

Finland

Consecutive incident cases diagnosed at the Oulu

University Hospital between 2000-2004

Female blood donors recruited in 2002 from the

same geographical region in Northern Finland

OFBCR Ontario Familial Breast

Cancer Registry 31

Canada

Invasive cases aged 20-54 years

identified from the Ontario Cancer Registry from

1996-1998. All those at high genetic risk were

eligible; random samples of women not meeting

these criteria were also asked to participate.

Identified by calling randomly selected residential

telephone numbers in the same geographical region

from 1998-2001; frequency matched to cases by age

in 5 year categories

ORIGO

Leiden University

Medical Centre Breast

Cancer Study 33, 34

Netherlands

Consecutive case patients diagnosed 1996–2006 in

2 hospitals in South–West Netherlands (Leiden &

Rotterdam). No selection for family history;

Rotterdam case patients selected for diagnosis aged

<70. Case patients with in situ carcinomas eligible.

(1) Blood bank healthy donors from Southwest

Netherlands recruited in 1996, 2000 or 2007; (2)

People who married a person who was part of a

family with high breast cancer risk (BRCA1/2/x).

From the Southwest of the Netherlands, recruited

1990–1996; (3) Females tested at the local clinical

genetics department for familial diseases, excluding

familial cancer syndromes (no mutation found in

gene(s) related to the disease being tested), recruited

1995–2007.

PBCS NCI Polish Breast

Cancer Study 35

Poland

Incident cases identified through a rapid

identification system in participating hospitals

covering ~ 90% of all eligible cases, and cancer

registries in Warsaw and Łódź covering 100% of all

eligible cases (2000-2003)

Randomly selected from population lists of all

residents of Poland from 2000-2003, stratified and

frequency matched to cases on city and age in 5-

year categories


RBCS Rotterdam Breast

Cancer Study 36

Netherlands

Familial breast cancer patients selected from the

clinical genetics center at Erasmus Medical Center

between 1994-2005

Spouses or mutation-negative siblings of

heterozygous Cystic Fibrosis mutation carriers

selected from the clinical genetics centre at Erasmus

Medical Center between 1996-2006

SASBAC Singapore and Sweden


Sweden

Women diagnosed in Sweden aged 50-74 in 1993-

1995

Population-based controls frequency matched by

age to the caases

SBCS Sheffield Breast

Cancer Study 38

U.K.

Women with breast cancer recruited in 1998-2005 at

surgical outpatient clinics at the Royal Hallamshire

Hospital, Sheffield

Unselected women attending the Sheffield

Mammography Screening Service in 2000-2004

with no evidence of a breast lesion

SEARCH

Study of Epidemiology

& Risk Factors in

Cancer Heredity 39

U.K.

Identified through the East Anglian Cancer

Registry: (i) 1991-1996: alive, prevalent cases

diagnosed before age 55; (ii) since 1996: incident

cases diagnosed before age 70 diagnosed after 1996

(a) Women from the same geographic region

selected from the EPIC-Norfolk cohort study, 1992-

1994 (b) women attending GP practices, frequency

matched to cases by age and geographic region

(2003-present)


SZBCS IHCC-Szczecin Breast

Cancer Study 40

Poland

Prospectively ascertained cases of invasive breast

cancer patients diagnosed at the Regional Oncology

Hospital (2002-2003 and 2006-2007) or the

University Hospital (2002-2007), both in Szczecin,

West Pomerania, Poland.

Selected from a population-based study of the 1.3

million inhabitants of West Pomerania (2003-2004);

matched to cases for year of birth, sex and region

UCIBCS UCI Breast Cancer

Study 41

U.S.A.

All cases diagnosed in Orange County, California

from 1994-1995; ascertained through the

population-based Cancer Surveillance Program of

Orange County California (CSPOC)

Recruited from 1998-2003 using random digit

dialling among Orange County residents; frequency

matched to cases by age and race/ethnicity

UKBGS Breakthrough

Generations Study UK

All cohort members who had had breast cancer or in

situ breast cancer before entry into the Breakthrough

Generations Study (cohort of >100,000 women

followed up for breast cancer, recruited from the

UK during 2003-2011).

Women who had not had breast cancer or in situ

breast cancer before entry into the cohort study

selected by 1:1 matching to cases on date of birth,

year of entry in to the study (2003-2009) source of

recruitment, blood sample and ethnicity.

STUDIES OF ASIAN WOMEN

ACP Asian Cancer Project Thailand

Cases from oncology centres in Thailand that

underwent biopsy and had been pathologically

diagnosed as having breast cancer.

Hospital based controls are women who were

admitted to the same hospital as the cases with

diseases not related to cancer or metabolic

syndromes such as diabetes, heart diseases or

conditions related to gynaecology.

SEBCS Seoul Breast Cancer

Study 42

South Korea

Consecutive, incident, cases from 2 hospitals in

Seoul recruited between 2001-2005

Women from same catchment area and participating

in annual health check-up (2001-2005)

TWBCS Taiwanese Breast

Cancer Study 43

Taiwan

Incident cases diagnosed & treated at 2 major

teaching hospitals in Taiwan between 2002-2005

Randomly selected women attending a health

examination at same hospitals between 2002-2005


Supplementary Note

Acknowledgements

The UK2 GWAS was funded by Wellcome Trust and Cancer Research UK. It included

samples collected through the FBCS study which is funded by Cancer Research UK

[C8620/A8372]. The WTCCC was funded by the Wellcome Trust. BCAC is funded by CR-

UK [C1287/A10118, C1287/A12014] and by the European Community's Seventh Framework

Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS).

Meetings of the BCAC have been funded by the European Union COST programme

[BM0606]. DFE is a Principal Research Fellow of Cancer Research UK. MG was supported

by the Lebanese National Council for Scientific Research. The ABCFS study was supported

by the National Health and Medical Research Council of Australia, the New South Wales

Cancer Council, the Victorian Health Promotion Foundation (Australia), and the National

Cancer Institute, National Institutes of Health under RFA-CA-06-503 and through

cooperative agreements with members of the Breast Cancer Family Registry (CFR) and PI’s.

The University of Melbourne (U01 CA69638) contributed data to this study. The content of

this manuscript does not necessarily reflect the views or the policies of the National Cancer

Institute or an of the collaborating centres in the CFR, nor does mention of trade names,

commercial products or organizations imply endorsement by the US Government or the CFR.

We extend our thanks to the many women and their families that generously participated in

the Australian Breast Cancer Family Study and consented to us accessing their pathology

material. JLH is a National Health and Medical Research Council Australia Fellow. MCS is

a National Health and Medical Research Council Senior Research Fellow. JLH and MCS are

both group leaders of the Victoria Breast Cancer Research Consortium. The ABCS is funded

by grants from the Dutch Cancer Society [NKI 2007-3839] and the Dutch National Genomics

Initiative. MKS is supported by the Dutch Cancer Society [NKI 2009-4363]. The ABCS

would like to acknowledge Sten Cornelissen, Richard van Hien, Linde Braaf , Laura Van’t

Veer (NKI-AVL), and Bas Bueno-de-Mesquita for the release of control samples as well as

Sander Canisius. The BBCS is funded by Cancer Research UK and Breakthrough Breast

Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the

National Cancer Research Network (NCRN). The BBCS GWAS received funding from The

Institut National de Cancer. The work of the BBCC was partly funded by ELAN-Fond of the

University Hospital of Erlangen. ES (BIGGS) is supported by NIHR Comprehensive


Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with

King's College London. IT is supported by the Oxford Biomedical Research Centre. We thank

Niall McInerney, Gabrielle Colleran, Andrew Rowan and Nicola Miller for their support. The

BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz society and

the German Cancer Research Center (DKFZ). We thank Anne Langheinz for genotyping. The

CECILE study was funded by Fondation de France [contract grant number 2004012618 and

2007005156] ; Institut National du Cancer (INCa) [2007-1/SPC2, 2008-1-CP-4 and 2009-1-

SHS/SP-04], Association pour la Recherche contre le Cancer (ARC) [2008-1-CP-4] ; Agence

Française de Sécurité Sanitaire de l’Environnement et du Travail (AFSSET - ANSES) [ST-

2005-003, EST2008/1/26, and VS-2009-21]; Ligue contre le Cancer Grand Ouest. The CGPS

was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish

Medical Research Council and Herlev Hospital. The CNIO-BCS was supported by the

Genome Spain Foundation, the Red Temática de Investigación Cooperativa en Cáncer and

grants from the Asociación Española Contra el Cáncer and the Fondo de Investigación

Sanitario (PI081583 and PI081120). We acknowledge the support of José Ignacio Arias

Pérez, Pilar Zamora, Primitiva Menendez, Tais Moreno and Guillermo Pita. The CTS was

supported by National Cancer Institute grant #CA 77398. The DFBBCS GWAS was funded

by The Netherlands Organisation for Scientific Research (NWO) as part of a ZonMw/VIDI

grant number 91756341. We thank Muriel Adank for selecting the samples and Margreet

Ausems, Christi van Asperen, Senno Verhoef, and Rogier van Oldenburg for providing

samples from their Clinical Genetic centers. The ESTHER study was supported by a grant

from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were

recruited in the context of the VERDI study, which was supported by a grant from the

German Cancer Aid (Deutsche Krebshilfe). The GC-HBOC was supported by Deutsche

Krebshilfe [107054], the Dietmar-Hopp Foundation, the Helmholtz society and the German

Cancer Research Centre (DKFZ). The GC-HBOC GWAS was supported by the German

Cancer Aid (grant no. 107352). GENICA was funded by the Federal Ministry of Education

and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and

01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum

(DKFZ), Heidelberg, Institute for Prevention and Occupational Medicine of the German

Social Accident Insurance (IPA), Bochum, as well as the Department of Internal Medicine,

Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The

following investigators participate in the GENICA Network: Dr. Margarete Fischer-Bosch-

Institute of Clinical Pharmacology, Stuttgart; University of Tübingen, Germany (CJ, HB),


Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ),

Heidelberg, Germany (Ute Hamann); Department of Internal Medicine, Evangelische

Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany (Yon-Dschun Ko,

Christian Baisch), Institute of Pathology, University of Bonn, Bonn, Germany (Hans-Peter

Fischer); Institute for Prevention and Occupational Medicine of the German Social Accident

Insurance (IPA), Bochum, Germany (TB, Beate Pesch, Sylvia Rabstein, Volker Harth). The

GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and genotyping in part by

the state of Baden-Württemberg through the Medical Faculty of the University of Ulm

[P.685]. HABCS has been supported by the Rudolf Bartling Foundation. The HEBCS study

has been financially supported by the Helsinki University Central Hospital Research Fund,

Academy of Finland (132473), the Finnish Cancer Society, The Nordic Cancer Union and the

Sigrid Juselius Foundation. The population allele and genotype frequencies were obtained

from the data source funded by the Nordic Center of Excellence in Disease Genetics based on

samples regionally selected from Finland, Sweden and Denmark. We thank Drs. Kirsimari

Aaltonen, Päivi Heikkilä, Tuomas Heikkinen and Dario Greco and RN Hanna Jäntti and Irja

Erkkilä for their help with the HEBCS data and samples. HMBCS has been supported by

fellowships to N.B. from the German Academic Exchange Program, DAAD, and from the

Friends of Hannover Medical School. HUBCS has been supported by a grant from the

German Federal Ministry of Research and Education, BMBF (RUS08/017). KARBAC is

supported by the Swedish Cancer Society, the Stockholm Cancer Society, the Gustav V

Jubilee foundation and the Bert von Kantzow foundation. The KBCP was financially

supported by the special Government Funding (EVO) of Kuopio University Hospital grants,

Cancer Fund of North Savo, the Finnish Cancer Organizations, The Academy of Finland and

by the strategic funding of the University of Eastern Finland. We thank Helena Kemiläinen,

Eija Myöhänen and Aija Parkkinen. kConFab is supported by grants from the National

Breast Cancer Foundation, the NHMRC, the Queensland Cancer Fund, the Cancer Councils

of New South Wales, Victoria, Tasmania and South Australia and the Cancer Foundation of

Western Australia. The kConFab Clinical Follow Up Study was funded by the NHMRC

[145684, 288704, 454508]. Financial support for the AOCS was provided by the United

States Army Medical Research and Materiel Command [DAMD17-01-1-0729], the Cancer

Council of Tasmania and Cancer Foundation of Western Australia and the NHMRC

[199600]. G.C.T. and P.W. are supported by the NHMRC. LMBC is supported by the

'Stichting tegen Kanker' (232-2008 and 196-2010). The MARIE study was supported by the

Deutsche Krebshilfe e.V. [70-2892-BR I], the Hamburg Cancer Society, the German Cancer


Research Center and the genotype work in part by the Federal Ministry of Education and

Research (BMBF) Germany [01KH0402]. MARIE would like to thank Tracy Slanger and

Elke Mutschelknauss for their valuable contributions, and S. Behrens, R. Birr, M.Celik, U.

Eilber, B. Kaspereit, N. Knese and K. Smit for their excellent technical assistance. MBCSG is

supported by a grant from Associazione Italiana per la Ricerca sul Cancro (4017) and funds

from Italian citizens who allocated the 5/1000 share of their tax payment in support of the

Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional

strategic projects “5x1000). MBCSG thanks Paolo Radice, Bernard Peissel, Monica Barile,

Marco A. Pierotti and the personnel of the Cancer Genetics Test laboratory. MCBCS was

supported by National Institutes of Health grant CA122340 and a Specialized Program of

Research Excellence (SPORE) in Breast Cancer (CA116201), and grants from the Komen

Foundation for the Cure and the Breast Cancer Research Foundation (BCRF). MCCS cohort

recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further

supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure

provided by Cancer Council Victoria. The NBCS was supported by grants from the

Norwegian Research council, 155218/V40, 175240/S10 to ALBD, FUGE-NFR 181600/V11

to VNK and a Swizz Bridge Award to ALBD. The NC-BCFR and OFBCR work was

supported by the United States National Cancer Institute, National Institutes of Health (NIH)

under RFA-CA-06-503 and through cooperative agreements with members of the Breast

Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario

(U01 CA69467), and Northern California Cancer Center (U01 CA69417). The content of this

manuscript does not necessarily reflect the views or policies of the National Cancer Institute

or any of the collaborating centers in the BCFR, nor does mention of trade names,

commercial products, or organizations imply endorsement by the US Government or the

BCFR. Samples from the NC-BCFR were processed and distributed by the Coriell Institute

for Medical Research. We thank Teresa Selander, Mona Gill, Lucine Collins, Nayana

Weerasooriya and members of the Ontario Familial Breast Cancer Registry (OFBCR) for

contributions to the study. OBCS is funded by the Finnish Cancer Foundation, The Academy

of Finland, the University of Oulu, Biocenter Oulu, the Oulu University Hospital. OBCS

acknowledges the assistance of Mervi Grip, Kari Mononen and Meeri Otsukka. ORIGO was

funded by grants from the Dutch Cancer Society (UL1997-1505) and the Biobanking and

Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). We thank E. Krol-

Warmerdam, and J. Blom. The PBCS was funded by Intramural Research Funds of the

National Cancer Institute, Department of Health and Human Services, USA. The RBCS was


funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC

study was supported by funding from the Agency for Science, Technology and Research of

Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen

Breast Cancer Foundation. SBCS was funded by Yorkshire Cancer Research. SEARCH is

funded by grants from Cancer Research UK [C8197/A10123, C8197/A10123 and

C490/A10124]. AMD has been supported by Cancer Research UK grant [C8197/A10865] and

by the Joseph Mitchell Fund. SZBCS was supported by Grant PBZ_KBN_122/P05/2004;

Katarzyna Jaworska is a fellow of International PhD program, Postgraduate School of

Molecular Medicine, Warsaw Medical University, supported by the Polish Foundation of

Science. The UCIBCS component of this research was supported by the NIH [CA58860,

CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS was funded by

Breakthrough Breast Cancer and the Institute of Cancer Research. We thank the study

participants, health staff, and BGS study team members who contributed to the blood sample

and data collection. The Institute of Cancer Research acknowledges NHS funding to the

NIHR Biomedical Research Centre. The ACP study is funded by the Breast Cancer Research

Trust, UK. The ACP study wishes to thank the participants in the Thai Breast Cancer study.

Special thanks also go to the Thai Ministry of Public Health (MOPH), doctors and nurses who

helped with the data collection process. The study would like to thank Dr Prat

Boonyawongviroj, the former Permanent Secretary of MOPH and Dr Pornthep

Siriwanarungsan, the Department Director-General of Disease Control who have supported

the study throughout. The SEBCS was supported by the Korea Health 21 R&D Project

[AO30001], Ministry of Health and Welfare, Republic of Korea. The TWBCS is supported

by the Taiwan Biobank project of the Institute of Biomedical Sciences, Academia Sinica,

Taiwan. CGEMS. The Nurses’ Health Studies are supported by NIH grants CA 65725,

CA87969, CA49449, CA67262, CA50385 and 5UO1CA098233.


Consortia Membership

Australian Ovarian Cancer Study Group

David D Bowtell, Adele C Green, Georgia Chenevix-Trench, Anna deFazio,

Dorota Gertig, Penelope M Webb.

FBCS (Breast Cancer Susceptibility Collaboration UK)

A. Ardern-Jones, J. Adlard, G. Attard, K. Bailey, E. Bancroft, C. Bardsley, D. Barton, J. Barwell,

L. Baxter, R. Belk, J. Berg, T. Bishop, L. Boyes, N. Bradshaw, A. Brady, S. Brant, C. Brewer, G.

Brice, G. Bromilow, C. Brooks, A. Bruce, B. Bulman, L. Burgess, J. Campbell, B. Castle, R.

Cetnarskyj, C. Chapman, O. Claber, N. Coates, T. Cole, A. Collins, J. Cook, S. Coulson, G.

Crawford, D. Cruger, C. Cummings, L. D’Mello, R. Davidson, L. Day, L. de Silva, B. Dell, C.

Dolling, A. Donaldson, A. Donaldson, H. Dorkins, F. Douglas, S. Downing, S. Drummond, J.

Dunlop, S. Durrell, D. Eccles, C. Eddy, M. Edwards, E. Edwards, J. Edwardson, R. Eeles, I.

Ellis, F. Elmslie, G. Evans, B. Gibbens, C. Gardiner, C. Giblin, S. Gibson, S. Goff, S. Goodman,

D. Goudie, L. Greenhalgh, J. Greer, H. Gregory, D. Halliday, R. Hardy, C. Hartigan, T. Heaton,

A. Henderson, C. Higgins, S. Hodgson, T. Holt, T. Homfray, D. Horrigan, C. Houghton, R.S.

Houlston, L. Hughes, V. Hunt, L. Irvine, L. Izatt, L. Jackson, C. Jacobs, S. James, M. James, L.

Jeffers, I. Jobson, W. Jones, M.J. Kennedy, S. Kenwrick, C. Kightley, C. Kirk, L. Kirk, E.

Kivuva, A. Kumar, F. Lalloo, N. Lambord, C. Langman, P. Leonard, S. Levene, S. Locker, P.

Logan, M. Longmuir, A. Lucassen, V. Lyus, A. Magee, A. Male, S. Mansour, D. McBride, E.

McCann, V. McConnell, M. McEntagart, K. McDermot, C. McKeown, L. McLeish, D. McLeod,

L. Mercer, C. Mercer, Z. Miedzybrodzka, J. Miller, A. Mitra, P. J. Morrison, V. Murday, A.

Murray, J. Myring, J. Paterson, P. Pearson, G. Pichert, K. Platt, M. Porteous, C. Pottinger, S.

Price, L. Protheroe, S. Pugh, O. Quarrell, C. Riddick, L. Robertson, A. Robinson, V. Roffey-

Johnson, M. Rogers, S. Rose, S. Rowe, A. Schofield, N. Rahman, G. Scott, J. Scott, A. Searle, S.

Shanley, S. Sharif, J. Shaw, J. Shea-Simonds, L. Side, J. Sillibourne, K. Simon, S. Simpson, S.

Slater, K. Smith, L. Snadden, J. Soloway, Y. Stait, B. Stayner, M. Steel, C. Steel, H. Stewart, D.

Stirling, M. Thomas, S. Thomas, S. Tomkins, H. Turner, E. Tyler, E. Wakeling, F. Waldrup, L.

Walker, C. Watt, S. Watts, A. Webber, C. Whyte, J. Wiggins, E. Williams, L. Winchester.

GENICA Network

Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University

Tübingen, Germany: Hiltrud Brauch, Christina Justenhoven;


Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg,

Germany: Ute Hamann;

Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus,

Bonn, Germany: Yon-Dschun Ko, Christian Baisch;

Institute of Pathology, Medical Faculty of the University of Bonn, Germany: Hans-Peter Fischer;

Institute for Prevention and Occupational Medicine of the German Social Accident

Insurance(IPA), Bochum, Germany: Thomas Bruening, Beate Pesch, Sylvia Rabstein, Volker

Harth;

Institute and Outpatient Clinic of Occupational Medicine, Saarland University Medical Center

and Saarland University Faculty of Medicine, Homburg, Germany: Volker Harth.

HEBON

Netherlands Cancer Institute, Amsterdam: Senno Verhoef, Martijn Verheus, Laura J. van

‘t Veer, Flora E. van Leeuwen;

Erasmus Medical Center, Rotterdam: Margriet Collée, Maartje J. Hooning, Madeleine

M.A. Tilanus-Linthorst, Caroline Seynaeve;

Leiden University Medical Center, Leiden: Christi J. van Asperen, Juul T. Wijnen, Rob A.

Tollenaar;

Radboud University Nijmegen Medical Center, Nijmegen: Marjolijn J. Ligtenberg;

University Medical Center Utrecht, Utrecht: Margreet G. Ausems;

Amsterdam Medical Center: Cora M. Aalfs, Theo A. van Os;

VU University Medical Center, Amsterdam: Johan J.P. Gille, Quinten Waisfisz;

University Hospital Maastricht, Maastricht: Cees E. van Roozendaal, Marinus J. Blok;

University Medical Center Groningen University: Jan C. Oosterwijk, Annemarie H van

der Hout, Marian J. Mourits;

The Netherlands Foundation for the detection of hereditary tumours, Leiden: Hans F.

Vasen.

kConFab

Research Centre, Prince of Wales Hospital, Randwick, New South Wales:

Morteza Aghmesheh;

Genetic Health Services Victoria, Royal Children’s Hospital, Melbourne: David Amor;

Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick: Lesley Andrews, Barbara

Bennett64, Kathy Tucker, Janet Tyler, Bettina Meiser;

Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, St


Andrews Place, East Melbourne: Yoland Antill, Sarah-Jane Dawson, Kelly Phillips, Clare

Scott;

Anatomical Pathology, Royal Women’s Hospital, Carlton, Victoria: Jane Armes;

Molecular Genetics Laboratory, Royal Brisbane and Women’s Hospital, Herston,

Queensland: Shane Armitage, Leanne Arnold, Alison Jones;

Departments of Translational and Medical Oncology, Westmead Hospital, Westmead,

New South Wales: Rosemary Balleine;

Cancer Biology Laboratory, TVW Institute for Child Health Research, Subiaco, Western

Australia: Glenn Begley;

Pathology Centre, Queen Elizabeth Medical Centre, Nedlands, Western Australia: John

Beilby;

Silverton Place, Brisbane, Queensland: Ian Bennett;

Department of Public Health and Community Medicine, University of Sydney, Sydney:

Geoffrey Berry;

John Curtin School of Medical Research, Australian National University, Canberra:

Anneke Blackburn;

NSW Breast Cancer Institute, Westmead, New South Wales: Meagan Brennan;

Department of Biochemistry, University of Queensland, St. Lucia, Queensland: Melissa

Brown;

Molecular and Cytogenetics Unit, Prince of Wales Hospital, Randwick, New South

Wales: Michael Buckley;

Royal Hobart Hospital, Hobart, Tasmania: Jo Burke, Evelyn Humphrey;

Medical Psychology Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales:

Phyllis Butow;

Australian Genome Research Facility, Walter & Eliza Hall Medical Research Institute,

Royal Melbourne Hospital, Parkville, Victoria: Keith Byron;

Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide/Hanson

Institute, South Australia: David Callen;

Peter MacCallum Cancer Centre, St Andrew’s Place, East Melbourne, Victoria: Ian

Campbell, Joe Sambrook, Heather Thorne;

Queensland Institute of Medical Research, Herston, Queensland: Nick Hayward;

Westmead Institute for Cancer Research, University of Sydney, Westmead Hospital

,Westmead, New South Wales: Christine Clarke, Graham Mann;

Department of Clinical Genetics, Liverpool Health Service, Liverpool, New South Wales:


Alison Colley;

Mutation Research Centre, St Vincent’s Hospital, Fitzroy, Victoria: Dick Cotton;

Centre for Genetic Epidemiology, The University of Melbourne, Carlton, Victoria: Jisheng

Cui;

Molecular and Clinical Genetics, Royal Prince Alfred Hospital, Camperdown, New South

Wales: Bronwyn Culling;

Department of Pathology, University of Queensland Medical School, Herston, New

South Wales: Margaret Cummings;

Central Regional Genetic Services, Wellington Hospital, Wellington South, New Zealand:

Joanne Dixon;

Molecular Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne,

Victoria: Alexander Dobrovic, Paul Waring;

Hunter Genetics, Hunter Area Health Service, Waratah, New South Wales: Tracy

Dudding, Rodney Scott;

Clinical Chemistry, Princess Margret Hospital for Children, Perth, Western Australia: Ted

Edkins;

Department of Multicultural Health, University of Sydney, New South Wales: Maurice

Eisenbruch;

Tissue Pathology, Institute of Medical & Veterinary Science, Adelaide, South Australia:

Gelareh Farshid;

Family Cancer Clinic, Monash Medical Centre, Clayton, Victoria: Susan Fawcett;

Faculty of Medicine, Royal North Shore Hospital, St Leonards, New South Wales:

Michael Field;

Department of Haematology, Flinders Medical Centre, Bedford Park, South Australia:

Frank Firgaira, Scott Grist, Ram Seshadri;

Eskitis Institute of Cell & Molecular Therapies, School of Biomolecular and Biomedical

Sciences, Griffith University, Nathan, Queensland: Jean Fleming;

Surgical Oncology, University of Newcastle, Newcastle Mater Hospital, Waratah, New

South Wales: John Forbes;

Department of Medical Oncology, Prince of Wales Hospital, Randwick, New South

Wales: Michael Friedlander100;

Victorian Clinical Genetics Service, Royal Melbourne Hospital, Parkville, Victoria: Clara

Gaff, Mac Gardner;

Queensland Clinical Genetic Service, Royal Children’s Hospital, Herston, Queensland:


Mike Gattas;

Clinical Biochemistry Unit, Canterbury Health Labs, Christchurch, New Zealand: Peter

George;

ancer Epidemiology Centre, The Cancer Council Victoria, Carlton, Victoria: Graham

Giles;

Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia: Grantley

Gill;

Genetic Services of WA, King Edward Memorial Hospital, Subiaco, Western Australia:

Jack Goldblatt, Sharron Townshend, Ian Walpole;

Wollongong Hereditary Cancer Clinic, Wollongong Public Hospital, New South Wales:

Sian Greening;

Department of Medical Genetics, Women’s and Children’s Hospital, North Adelaide,

South Australia: Eric Haan, Graeme Suthers;

Familial Cancer Clinic, Peter MacCallum Cancer Centre, East Melbourne, Victoria:

Marion Harris, Michael McKay, Gillian Mitchell, Mary Ann Young;

Breast and Ovarian Cancer Genetics, Monash Medical Centre, Bentleigh East, Victoria:

Stewart Hart;

Centre for Molecular Environmental, Genetic & Analytic Epidemiology, University of

Melbourne, Melbourne, Victoria: John Hopper, Richard Osborne;

School of Population Health, The University of Melbourne, Carlton, Victoria: Mark

Jenkins;

Medical Oncology, Westmead Hospital, Westmead, New South Wales: Rick Kefford113;

Familial Cancer Service, Department of Medicine, Westmead Hospital, Westmead, New

South Wales: Judy Kirk, Jennifer Leary;

Breast Endocrine and Surgical Unit, Royal Adelaide Hospital, North Terrace, South

Australia: James Kollias;

Molecular Pathology Department, Southern Cross Pathology, Monash Medical Centre,

Clayton, Victoria: Sergey Kovalenko;

Molecular and Cellular Pathology, The University of Queensland, Herston, Queensland:

Sunil Lakhani;

Department of Psychological Medicine, Royal North Shore Hospital, St Leonards, New

South Wales: Jacqueline Lim, Christopher Tennant;

Breast Cancer Laboratory, Walter and Eliza Hall Institute, PO Royal Melbourne Hospital,

Parkville, Victoria: Geoff Lindeman;


Medical Oncology and Clinical Haematology Unit, Western Hospital, Footscray, Victoria:

Lara Lipton;

WA Centre for Cancer, Edith Cowan University, Churchlands, Western Australia: Liz

Lobb;

Department of Psychological Medicine, University of Sydney, New South Wales:

Mariette Maclurcan, Melanie Price;

Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New

South Wales: Deborah Marsh;

Cancer Epidemiology Research Unit, NSW Cancer Council, Woolloomooloo, New South

Wales: Margaret McCredie;

Department of Oncology, St Vincent’s Hospital, Fitzroy, Victoria: Sue Anne McLachlan;

School of Public Health, Queensland University of Technology, Kelvin Grove,

Queensland: Beth Newman;

St Vincent’s Breast Clinic, Toowoomba, Queensland: Imelda O’Loughlin, Graham

Warren, Elizabeth Watson;

Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria: Lester

Peters;

Genetic Services, Auckland Hospital, Auckland, New Zealand: Jeanne Reeve, Ingrid

Winship;

Cancer Genetics Laboratory, University of Otago, Dunedin, New Zealand: Tony Reeve;

Department of Cytogenetics and Molecular Genetics, Women and Children’s Hospital,

Adelaide, South Australia: Robert Richards;

Hancock Family Breast Cancer Foundation, West Perth, Western Australia: Gina

Rinehart;

Oncology Service, Christchurch Hospital, Christchurch, New Zealand: Bridget Robinson;

Molecular Pathology Institute of Medical and Veterinary Science, Adelaide, South

Australia: Barney Rudzki;

Section of Cytology, Institute of Clinical Pathology and Medical Research, Westmead

Hospital, Westmead, New South Wales: Elizabeth Salisbury;

School of Surgery and Pathology, QE11 Medical Centre, Nedlands, Western Australia:

Christobel Saunders;

South View Clinic, Kogarah, New South Wales: Elizabeth Scott;

Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New

Zealand: Andrew Shelling;


Department of Radiology, Royal Perth Hospital, Perth, Western Australia: Donna Taylor;

Murdoch Institute, Royal Children’s Hospital, Parkville, Victoria: Deon Venter;

Molecular Genetics of Cancer Division, Walter & Eliza Hall Medical Research Institute,

Royal Melbourne Hospital, Parkville, Victoria: Jane Visvader;

Department of Medical Oncology, St Vincents Hospital, Darlinghurst, New South Wales:

Robin Ward;

Cabrini Hospital, Malvern, Victoria: Bev Warner;

Family Cancer Clinic, St Vincent’s Hospital, Darlinghurst, New South Wales: Rachael

Williams;

Medical Psychology Research Unit, Royal North Shore Hospital, St Leonards, New

South Wales: Judy Wilson.


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supplementary table 1 - media.nature.com · 51saarland cancer registry, saarbrücken, germany....

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