Hum Mol Genet. Dec 1, 2011; 20(23): 4693–4706.
Published by Oxford University Press 2011
Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium†
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA,
2Sections of Epidemiology and Genetics, and
3Section of Cancer Genetics, The Institute of Cancer Research, Sutton, UK,
4United Kingdom Department of Oncology and Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
5Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Genetic and Analytic Epidemiology, and
6Department of Pathology, The University of Melbourne, Melbourne, Vic, Australia
7Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands,
8Leiden University Medical Center, Leiden, The Netherlands,
9Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA,
10Department of Gynecology and Obstetrics, University Hospital Erlangen, and
11Institute of Human Genetics, Friedrich-Alexander University, Erlangen, Germany,
12Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel St., London, UK,
13Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK,
14National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's and St. Thomas’ NHS Foundation Trust in partnership with King's College London, London, UK,
15NHS Foundation Trust, King's College Hospital, London, UK,
16Welcome Trust Centre for Human Genetics and Oxford Comprehensive Biomedical Research Centre, University of Oxford, UK,
17Clinical Science Institute. University Hospital Galway, Galway, Ireland,
18Department of Obstetrics and Gynecology, and
19National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany,
20Molecular Epidemiology Group,
21Division of Clinical Epidemiology and Aging Research, and
22Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany,
23Department of Clinical Biochemistry, Copenhagen University Hospital, and
24Department of Breast Surgery, Copenhagen University Hospital, Herlev Hospital, Denmark,
25Cancer Research Group, Human Genetics Programme, and
26Genetic and Molecular Epidemiology Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain,
27Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain,
28Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain,
29Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Germany,
30Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, Germany,
31Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany,
32Institute of Pathology, University of Bonn, Bonn, Germany,
33Deutsches Krebsforschungszentrum (DKFZ), Molecular Genetics of Breast Cancer, Heidelberg, Germany,
34Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany,
35Gynecology Research Unit,
36Clinics of Radiation Oncology,
37Clinics of Obstetrics and Gynecology,
38Gynecology Research Unit and Clinics of Radiation Oncology, and
39Clinics of Radiation Oncology, Hannover Medical School, Hannover, Germany,
40Department of Obstetrics and Gynecology
41Department of Clinical Genetics, and
42Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland,
43Belarusian Institute for Oncology and Medical Radiology, Minsk, Belarus,
44Department of Pathology, Belarusian Medical Academy of Post-Graduate Education, Minsk, Belarus,
45Institute of Biochemistry and Genetics, and
46Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Science, Ufa, Russia,
47Department of Surgery and Oncology, Bashkir State Medical University, Ufa, Russia,
48Karolinska Institute, Stockholm, Sweden,
49Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm,
50Queensland Institute of Medical Research, Herston, Australia,
51Genetics and Population Health Division, Queensland Institute of Medical Research, Herston, Brisbane, Australia,
52The Kathleen Cuningham Foundation for Resesarch into Familial Breast Cancer (kConFab), Peter MacCallum Cancer Centre, East Melbourne, Australia,
53Institute of Clinical Medicine, Pathology and Forensic Medicine, and
54Institute of Clinical Medicine, Oncology, University of Eastern Finland, Biocenter Kuopio, Kuopio, Finland,
55Department of Pathology, Cancer Center of Eastern Finland, and
56Department of Oncology, Cancer Center of Eastern Finland, Kuopio University Hospital, Kuopio, Finland,
57Vesalius Research Center, VIB and University of Leuven, Leuven, Belgium,
58Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium,
59Department of Preventive and Predictive Medicine, Unit of Molecular Bases of Genetic Risk and Genetic Testing, and
60Department of Preventive and Predictive Medicine, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy,
61IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy,
62Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy,
63Department of Laboratory Medicine and Pathology, and
64Department of Pharmacology, Mayo Clinic, Rochester, MN, USA,
65Cancer Epidemiology Centre, Cancer Council, Victoria, Australia,
66Department of Anatomical Pathology, Alfred Hospital, Victoria, Australia,
67Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, Cornell Weill Medical College, New York, NY, USA,
68American Cancer Society, Genetic Epidemiology Unit, Atlanta, GA, USA,
69Cancer Prevention Institute of California, Fremont, CA, USA,
70Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA,
71Department of Clinical Genetics, Laboratory of Cancer Genetics and Biocenter Oulu, Oulu University Hospital,
72Department of Oncology, Oulu University Hospital, and
73Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland,
74Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Prosserman Centre for Health Research, Toronto, Canada,
75Department of Molecular Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada,
76Department of Laboratory Medicine, St. Michael's Hospital and the University of Toronto, Toronto, Canada,
77Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada,
78Department of Laboratory Medicine and the Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Canada,
79Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland,
80Department of Medical Oncology, Family Cancer Clinic,
81Department of Medical Oncology, Josephine Nefkens Institute, and
82Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands,
83Dept of Oncology, Faculty of Medicine, Dentistry and Health, and
84Department of Neuroscience, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK,
85Seoul National University College of Medicine, Soul, Korea,
86University of Ulsan College of Medicine, Asan Medical Center, Soul, Korea,
87Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland,
88National Cancer Institute, Bangkok, Thailand,
89International Agency for Research on Cancer, Lyon, France,
90Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan,
91Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan,
92Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan,
93Department of Epidemiology, School of Medicine, University of California Irvine, Irvine, CA, USA,
94University of Wisconsin Carbone Cancer Center, Madison, WI, USA,
95Division of Population Sciences, Moffitt Cancer Center and Research Institute, Tampa, FL, USA,
96Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington DC, USA, and
97Department of Community and Family Medicine, and
98Department of Pediatrics, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, USA
Received July 6, 2011; Revised July 6, 2011; Accepted August 15, 2011.
FUNDING AND ACKNOWLEDGEMENTS
The Breast Cancer Association Consortium (BCAC) was supported by Cancer Research UK grant C1287/A12014. D.F.E. is a Principal Research Fellow of Cancer Research UK.
The ABCFS was supported by the National Health and Medical Research Council of Australia (NHMRC) , the NIH [CA102740-01A2], and by the United States National Cancer Institute, NIH [CA-95-011] through cooperative agreements with members of the Breast Cancer Family Registry and principal investigators Cancer Care Ontario [CA69467], Columbia University [CA69398], Fox Chase Cancer Center [CA69631], Huntsman Cancer Institute [CA69446], Northern California Cancer Center [CA69417] and University of Melbourne [CA69638]. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of collaborating centers in the Breast CFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the Breast CFR. The ABCFS was initially supported by the NHMRC, the New South Wales Cancer Council and the Victorian Health Promotion Foundation. J.L.H. is an Australia Fellow of the NHMRC and Victorian Breast Cancer Research Consortium Group Leader. M.C.S. is a Senior Research Fellow of the NHMRC and Victorian Breast Cancer Research Consortium Group Leader. This research was supported by the Victorian Government through Victorian Cancer Agency funding of the Victorian Breast Cancer Research Consortium.
The ABCS study was supported by the Dutch Cancer Society [grants NKI 2001–2423; 2007–3839] and the Dutch National Genomics Initiative. ABCS acknowledges the Family Cancer Clinic at the NKI-AVL and Richard van Hien and Sten Cornelissen for DNA plating.
The BBCC study was partly funded by the ELAN Funding of the University of Erlangen.
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 BSUCH study was supported by the Dietmar-Hopp Foundation and the Helmholtz Society.
The CGPS Funding: The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital. Acknowledgements: We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out.
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 Cáncer and the Fondo de Investigación Sanitario [PI081120 to J.B., PI081583 to R.L.M.]. We thank Charo Alonso, Tais Moreno, Guillermo Pita, Primitiva Menendez and Anna González-Neira.
FBCS Cancer Research UK (C8620/A83); US Military Acquisition (ACQ) Activity, Era of Hope Award (W81XWH-05–1–0204) The samples were collected and screened for BRCA mutations through funding from Cancer Research UK; US Military Acquisition (ACQ) Activity, Era of Hope Award (W81XWH-05–1–0204) and the Institute of Cancer Research (UK). This study makes use of data generated by the Wellcome Trust Case Control Consortium (WTCCC) 2. A full list of the investigators who contributed to the generation of the data is available from the WTCCC website. C.T. is funded by a Medical Research Council (UK) Clinical Research Fellowship.
The GENICA study was supported by the German Human Genome Project and funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114. Genotyping analyses were supported by Robert Bosch Foundation of Medical Research, Stuttgart, Germany. The GENICA network would also like to acknowledge 1. Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Germany; [C.J., H.B.]; 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 [Hand-Peter Fischer]. Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [Ute Hamann]; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, Germany [TB, Beate Pesch, Sylvia Rabstein, Volker Harth].
The GESBC study was supported by the Deutsche Krebshilfe e. V.  and GESBC genotyping in part by the state of Baden-Württemberg through the Medical Faculty of the University of Ulm [P.685].
The HABCS study was supported by an intramural grant from Hannover Medical School and by a grant from the German Research Foundation [DFG, Do761/2–1].
The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation.
HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017).
The KARBAC study was supported by The Swedish Cancer Society, The Stockholm Cancer Society, The Gustav V Jubilee Foundation and The Bert von Kantzow Foundation.
: kConFab (the Kathleen Cuningham Consortium for Research into Familial Breast Cancer) thanks Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow-Up Study (funded by NHMRC grants 145684
) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. The Australian Ovarian Cancer Study (AOCS) Management Group (D. Bowtell, G. Chenevix-Trench, A. deFazio, D. Gertig, A. Green and P.M. Webb) gratefully acknowledges the contribution of all the clinical and scientific collaborators (see http://www.aocstudy.org/
). The Australian Cancer Study Management Group (A. Green, P. Parsons, N. Hayward, P.M.Webb, and D. Whiteman) thank all of the project staff, collaborating institutions and study participants. A.B.S. is an NHMRC Senior Research Fellow, and G.C.T. is an NHMRC Senior Principal Research Fellow.
The KBCP was supported by Grants from the Finnish Cancer Society; the Academy of Finland (grant number 127220); EVO Research Fund (grant number 5654113 and 5501); EVO research funding of Vaasa Hospital District (grant number 100449); and the strategic funding of the University of Eastern Finland. We thank Mrs. Helena Kemiläinen, Mrs Aija Parkkinen and Mrs. Eija Myöhänen for their skillful technical assistance.
The LMBC Leuven Multidisciplinary Breast Center (LMBC) is supported by the ‘Stichting tegen Kanker’ (232–2008). B.T.Y is funded by FWO. We acknowledge Gilian Peuteman, Dominiek Smeets, Thomas Van Brussel for technical support.
MBCSG is supported by grants from Ministero della Salute (Extraordinary National Cancer Program 2006 ‘Alleanza contro il Cancro’, and ‘Progetto Tumori Femminili’ to P.R.), Ministero dell'Universita’ e Ricerca (RBLAO3-BETH to P.R.), Fondazione Italiana per la Ricerca sul Cancro (Special Project ‘Hereditary tumors’), Associazione Italiana per la Ricerca sul Cancro (4017 and by 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 ‘‘5 × 1000’).
The MCBCS was supported by National Institutes of Health grant, R01 CA122340, and an NCI Specialized Program of Research Excellence (SPORE) in breast cancer, P50 CA116201.
The MCCS study was supported by Cancer Council Victoria and by NHMRC grants 209057, 251533, 396414, 504711 and 504715. The MEC study was supported by National Institutes of Health grants R01-CA63464 and R37-CA54281.
The MSKCC study was supported by the Breast Cancer Research Foundation, the Normal and Carol Stone Genetics Research Fund, and the Robert, the Robert and Kate Niehaus Clinical Genetics Initiative and the Lymphoma Foundation.
The NC-BCFR and OFBCR are funded by 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 (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), the Cancer Prevention Institute of California (formerly the Northern California Cancer Center, U01 CA69417) and the University of Melbourne (U01 CA69638). 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.
OBCS was supported by research grants from the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Academy of Finland, the University of Oulu, and the Oulu University Hospital.
The OFBCR was supported by 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 (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417) and University of Melbourne (U01 CA69638) and by Cancer Care Ontario. 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.
The PBCS was supported by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA.
The RBCS study was supported by Dutch Cancer Society: DDHK 2004-3124. RBCS would like to acknowledge Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens and Annette Heemskerk for their contribution in data management.
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.
The SBCS study Funding: Breast Cancer Campaign and Yorkshire Cancer Research. SBCS would like to acknowledge Helen Cramp, Sue Higham, Dan Connley and Saba Balasubramanian.
SEARCH study was supported by Cancer Research UK grants: C490/A1102, C8197/A10123, C490/A10119, C490/A11020, C1287/A10118 and A.M.D. was funded by CR-UK grant C8197/A10865. The pathology work in Cambridge was supported by the NIHR Cambridge Biomedical Research Centre and by the Cambridge Experimental Cancer Medicine Centre.
The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. K.J. is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University, supported by the Polish Foundation of Science.
The TBCS was funded by The National Cancer Institute Thailand.
The TWBCS study was supported by the Institute of Biomedical Sciences, Academia Sinica, National Sciences Council and Taiwan Biobank.
The UCIBCS study was supported by the National Institutes of Health, National Cancer Institute grants CA-58860 and the Lon V Smith Foundation grant LVS-39420.
The US3SS study was supported by Massachusetts (K.M.E., R01CA47305), Wisconsin (P.A.N., R01 CA47147) and New Hampshire (L.T.-E., R01CA69664) centers, and Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA.