Heterogeneity of Breast Cancer Associations with Five Susceptibility Loci by Clinical and Pathological Characteristics Montserrat Garcia-Closas 1 *, Per Hall 2 , Heli Nevanlinna 3 , Karen Pooley 4 , Jonathan Morrison 4 , Douglas A. Richesson 1 , Stig E. Bojesen 5,6 , Børge G. Nordestgaard 5 , Christen K. Axelsson 7 , Jose I. Arias 8,9 , Roger L. Milne 8 , Gloria Ribas 8 , Anna Gonza ´ lez-Neira 8 , Javier Benı´tez 8 , Pilar Zamora 10 , Hiltrud Brauch 11 , Christina Justenhoven 11 , Ute Hamann 12 , Yon-Dschun Ko 13 , Thomas Bruening 14 , Susanne Haas 15 , Thilo Do ¨ rk 16 , Peter Schu ¨ rmann 16 , Peter Hillemanns 16 , Natalia Bogdanova 16,17 , Michael Bremer 17 , Johann Hinrich Karstens 17 , Rainer Fagerholm 3 , Kirsimari Aaltonen 3,18 , Kristiina Aittoma ¨ki 19 , Karl von Smitten 20 , Carl Blomqvist 18 , Arto Mannermaa 21,22 , Matti Uusitupa 23 , Matti Eskelinen 24 , Maria Tengstro ¨m 25,26 , Veli-Matti Kosma 21,22 , Vesa Kataja 25,26 , Georgia Chenevix-Trench 27 , Amanda B. Spurdle 27 , Jonathan Beesley 27 , Xiaoqing Chen 27 , Australian Ovarian Cancer Management Group 27,28 , The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer 28 , Peter Devilee 29 , Christi J. van Asperen 30 , Catharina E. Jacobi 31 , Rob A. E. M. Tollenaar 32 , Petra E.A. Huijts 33 , Jan G. M. Klijn 33 , Jenny Chang-Claude 34 , Silke Kropp 34 , Tracy Slanger 34 , Dieter Flesch-Janys 35 , Elke Mutschelknauss 35 , Ramona Salazar 36 , Shan Wang-Gohrke 37 , Fergus Couch 38 , Ellen L. Goode 38 , Janet E. Olson 38 , Celine Vachon 38 , Zachary S. Fredericksen 38 , Graham G. Giles 39 , Laura Baglietto 39 , Gianluca Severi 39 , John L. Hopper 40 , Dallas R. English 40 , Melissa C. Southey 41 , Christopher A. Haiman 42 , Brian E. Henderson 42 , Laurence N. Kolonel 43 , Loic Le Marchand 43 , Daniel O. Stram 44 , David J. Hunter 45,46 , Susan E. Hankinson 46 , David G. Cox 46,47 , Rulla Tamimi 46 , Peter Kraft 47 , Mark E. Sherman 1 , Stephen J. Chanock 48 , Jolanta Lissowska 49 , Louise A. Brinton 1 , Beata Peplonska 50 , Jan G. M. Klijn 51 , Maartje J. Hooning 51 , Han Meijers-Heijboer 52 , J. Margriet Collee 52 , Ans van den Ouweland 52 , Andre G. Uitterlinden 53 , Jianjun Liu 54 , Low Yen Lin 54 , Li Yuqing 54 , Keith Humphreys 2 , Kamila Czene 2 , Angela Cox 55 , Sabapathy P. Balasubramanian 56 , Simon S. Cross 57 , Malcolm W. R. Reed 56 , Fiona Blows 4 , Kristy Driver 4 , Alison Dunning 4 , Jonathan Tyrer 4 , Bruce A. J. Ponder 58 , Suleeporn Sangrajrang 59 , Paul Brennan 60 , James McKay 60 , Fabrice Odefrey 60 , Valerie Gabrieau 60 , Alice Sigurdson 1 , Michele Doody 1 , Jeffrey P. Struewing 61 , Bruce Alexander 62 , Douglas F. Easton 4 , Paul D. Pharoah 4 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Marylan, United States of America, 2 Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden, 3 Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland, 4 Department of Oncology, University of Cambridge, Cambridge, United Kingdom, 5 Department of Clinical Biochemistry, Herlev and Bispebjerg University Hospitals, University of Copenhagen, Denmark, 6 Department of Bispebjerg University Hospitals, University of Copenhagen, Denmark, 7 Department of Breast Surgery, Herlev University Hospital, University of Copenhagen, Denmark, 8 Spanish National Cancer Centre, Madrid, Spain, 9 Monte Naranco Hospital, Oviedo, Spain, 10 La Paz Hospital, Madrid, Spain, 11 Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tu ¨ bingen, Tu ¨ bingen, Germany, 12 Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Germany, 13 Evangelische Kliniken Bonn gGmhH Johanniter Krankenhaus, Bonn, Germany, 14 Berufsgenossenschaftliches Forschungsinstitut fu ¨r Arbeitsmedizin, Ruhr University Bochum, Germany, 15 Institute fu ¨ r Pathology, University Bonn, Bonn, Germany, 16 Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany, 17 Department of Radiation Oncology, Hannover Medical School, Hannover, Germany, 18 Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland, 19 Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland, 20 Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland, 21 Institute of Clinical Medicine, Pathology and Forensic Medicine, Biocenter Kuopio, University of Kuopio, Kuopio, Finland, 22 Department of Pathology, Kuopio University Hospital, Kuopio, Finland, 23 Department of Public Health and Clinical Nutrition, Biocenter Kuopio, University of Kuopio, Kuopio, Finland, 24 Department of Surgery, Kuopio University Hospital, Kuopio, Finland, 25 Department of Oncology, Kuopio University Hospital, Kuopio, Finland, 26 Department of Oncology, Vaasa Central Hospital, Vaasa, Finland, 27 The Queensland Institute of Medical Research Post Office, Royal Brisbane Hospital, Herston, Queensland, Australia, 28 Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia, 29 Departments of Human Genetics and Pathology, Leiden University Medical Center, Leiden, The Netherlands, 30 Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands, 31 Department of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands, 32 Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands, 33 Department of Medical Oncology, Family Cancer Clinic, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands, 34 Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany, 35 Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany, 36 Bioglobe GmbH, Hamburg, Germany, 37 Molecular Biology Laboratory, Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany, 38 Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America, 39 Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Victoria, Australia, 40 Centre for MEGA Epidemiology, The University of Melbourne, Melbourne, Victoria, Australia, 41 Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia, 42 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America, 43 Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii, United States of America, 44 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America, 45 Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, 46 Channing Laboratory, Brigham and Women’s PLoS Genetics | www.plosgenetics.org 1 April 2008 | Volume 4 | Issue 4 | e1000054