A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11
Year: 2012
Type: review
Abstract: Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10(-8)) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10(-6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10(-9)), and with both ER-positive (OR = 1.09; P = 1.5 × 10(-5)) and ER-negative (OR = 1.16, P = 2.5 × 10(-7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/dds381
Authors: Afshan Siddiq, Fergus J. Couch, Gary K. Chen, Sara Lindström, Diana Eccles, Robert C. Millikan, Kyriaki Michailidou, Daniel O. Stram, Lars Beckmann, Suhn Kyong Rhie, Christine B. Ambrosone, Kristiina Aittomäki, Pilar Amiano, Carmel Apicella, Australian Breast Cancer Tissue Bank Investigators, Laura Baglietto, Elisa V. Bandera, Matthias W. Beckmann, Christine D. Berg, Leslie Bernstein, Carl Blomqvist, Hiltrud Brauch, Louise Brinton, Quang M. Bui, Julie E. Buring, Saundra S. Buys, Daniele Campa, Jane E. Carpenter, Daniel I. Chasman, Jenny Chang-Claude, Constance Chen, Françoise Clavel-Chapelon, Angela Cox, Simon S. Cross, Kamila Czene, Sandra L. Deming, Robert B. Diasio, W. Ryan Diver, Alison M. Dunning, Lorraine Durcan, Arif B. Ekici, Peter A. Fasching, Familial Breast Cancer Study, Heather Spencer Feigelson, Laura Fejerman, Jonine D. Figueroa, Olivia Fletcher, Dieter Flesch-Janys, Mia M. Gaudet, Susan M. Gerty, Jorge L. Rodriguez-Gil, Graham G. Giles, Carla H. van Gils, Andrew K. Godwin, Nikki Graham, Dario Greco, Per Hall, Susan E. Hankinson, Arndt Hartmann, Rebecca Hein, Judith Heinz, Robert N. Hoover, John L. Hopper, Jennifer J. Hu, Scott Huntsman, Sue A. Ingles, Astrid Irwanto, Claudine Isaacs, Kevin B. Jacobs, Esther M. John, Christina Justenhoven, Rudolf Kaaks, Laurence N. Kolonel, Gerhard A. Coetzee, Mark Lathrop, Loic Le Marchand, Adam M. Lee, I-Min Lee, Timothy Lesnick, Peter Lichtner, Jianjun Liu, Eiliv Lund, Enes Makalic, Nicholas G. Martin, Catriona A. McLean, Hanne Meijers-Heijboer, Alfons Meindl, Penelope Miron, Kristine R. Monroe, Grant W. Montgomery, Bertram Müller-Myhsok, Stefan Nickels, Sarah J. Nyante, Curtis Olswold, Kim Overvad, Domenico Palli, Daniel J. Park, Julie R. Palmer, Harsh Pathak, Julian Peto, Paul Pharoah, Nazneen Rahman, Fernando Rivadeneira, Daniel F. Schmidt, Rita K. Schmutzler, Susan Slager, Melissa C. Southey, Kristen N. Stevens, Hans-Peter Sinn, Michael F. Press, Eric Ross, Elio Riboli, Paul M. Ridker, Fredrick R. Schumacher, Gianluca Severi, Isabel dos Santos Silva, Jennifer Stone, Malin Sund, William J. Tapper, Michael J. Thun, Ruth C. Travis, Clare Turnbull, Andre G. Uitterlinden, Quinten Waisfisz, Xianshu Wang, Zhaoming Wang, JoEllen Weaver, Rüdiger Schulz-Wendtland, Lynne R. Wilkens, David Van Den Berg, Wei Zheng, Regina G. Ziegler, Elad Ziv, Heli Nevanlinna, Douglas F. Easton, David J. Hunter, Brian E. Henderson, Stephen J. Chanock, Montserrat Garcia-Closas, Peter Kraft, Christopher A. Haiman, Celine M. Vachon
Institutions: Imperial College London, University of Southampton, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, Institute for Quality and Efficiency in Health Care, Roswell Park Comprehensive Cancer Center, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, The University of Melbourne, Cancer Council Victoria, Rutgers Cancer Institute, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, City of Hope, Beckman Research Institute, Helsinki University Hospital, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Division of Cancer Epidemiology and Genetics, Brigham and Women's Hospital, Harvard University, University of Utah, Huntsman Cancer Institute, German Cancer Research Center, Inserm, Centre de recherche en Epidémiologie et Santé des Populations, Hôpital Paul-Brousse, University of Sheffield, Karolinska Institutet, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Mayo Clinic, American Cancer Society, University of Cambridge, University of California, Los Angeles, Kaiser Permanente, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, Institute of Cancer Research, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, University of Miami, Sylvester Comprehensive Cancer Center, University Medical Center Utrecht, University of Kansas Medical Center, University of Helsinki, Genome Institute of Singapore, Georgetown University, Georgetown Lombardi Comprehensive Cancer Center, National Cancer Institute, Science Applications International Corporation (United States), Cancer Prevention Institute of California, Stanford Cancer Institute, Stanford University, University of Hawaii Cancer Center, University of Southern California, Fondation Jean Dausset-CEPH, Helmholtz Munich, Institut für Humangenetik, UiT The Arctic University of Norway, QIMR Berghofer Medical Research Institute, The Alfred Hospital, Amsterdam UMC Location Vrije Universiteit Amsterdam, TUM Klinikum, Technical University of Munich, Dana-Farber Cancer Institute, Max Planck Institute of Psychiatry, Aalborg University Hospital, Aarhus University Hospital, Boston University, London School of Hygiene & Tropical Medicine, Erasmus MC, University of Cologne, University Hospital Heidelberg, USC Norris Comprehensive Cancer Center, Umeå University, University of Oxford, Fox Chase Cancer Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: Donald W. Reynolds Foundation, Amgen, University of Southern California, Wellcome Trust, Cancer Research UK, European Commission, Fondation Leducq, ZonMw, Ministerio de Economía y Competitividad, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Environmental Health Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1017297203, G1119724336, G1195446685, G121068745, G1253072103, G1345872088, G1364610698, G151562090, G153510172, G1569999668, G164076637, G2036036603, G2104425020, G2108445782, G215985982, G226745533, G229684361, G2313542652, Atypical Bacterial Infection as an Asthma Risk Factor, VITAMIN D RECEPTOR GENE POLYMORPHISM AND BREAST CANCER, Northern California Cooperative Family Registry for Breast Cancer, G2548880556, Biochemical Markers in the nurses' Health Study Cohort, G2646530656, G268454541, G2750880407, G299563851, G3083503531, GENETIC SUSCEPTIBILITY TO CANCER IN MULTIETHNIC COHORTS, G3276551827, G3283503243, AR and RUNX2 target genes in prostate cancer, G3426488059, G3489946217, G3552496254, G3602225402, G3652486217, G3695342494, G382329864, Dietary and Hormonal Determinants of Cancer in Women, G3968740382, G4028681359, G4063614301, G4258809411, Fine-mapping of 8q24 and Loci Identified in Genome-Wide Studies for Breast & Colo, G431899019, G443607800, G459566519, G464643678, G4666650047, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, G4724959105, G479225836, G4816767106, The Nashville Breast Health Study, G5362739798, G5528430224, G558986044, G5689392884, G5865683244, G589878898, G5935436683, G6008908520, Admixture Mapping for Breast Cancer in Latinas, G6279653796, G6283257732, G639206035, Race & Risk Factors for Early/Aggressive Breast Cancer, G6661458338, G6677215691, G6684135727, TRIAL OF ASPIRIN AND VITAMIN E IN WOMEN, G7166237062, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, Risk Factors for Breast Cancer in Younger Nurses, G7697152668, Biochemical Markers in the Nurses? Health Study Cohort, G77261304, Women's Health Study: Continued Follow-up, G8193320900, Premenopausal Hormone Levels and Risk of Breast Cancer, Collaborative Oncological Gene-environment Study, G870117454, G8790823546, University of Hawaii Cancer Center CCSG, UNC Center for Environmental Health and Susceptibility, Cancer Center Support Grant, G901085310, G921773184
OpenAlex ID: W2165084094