Genome-wide association studies identify four ER negative-specific breast cancer risk loci

Montserrat Garcia-Closas, Fergus J. Couch, Sara Lindstrom, Kyriaki Michailidou, Marjanka K. Schmidt, Mark N. Brook, Nick Orr, Suhn Kyong Rhie, Elio Riboli, Heather S. Feigelson, Loic Le Marchand, Julie E. Buring, Diana Eccles, Penelope Miron, Peter A. Fasching, Hiltrud Brauch, Jenny Chang-Claude, Jane Carpenter, Andrew K. Godwin, Heli NevanlinnaGraham G. Giles, Angela Cox, John L. Hopper, Manjeet K. Bolla, Qin Wang, Joe Dennis, Ed Dicks, Will J. Howat, Nils Schoof, Stig E. Bojesen, Diether Lambrechts, Annegien Broeks, Irene L. Andrulis, Pascal Guénel, Barbara Burwinkel, Elinor J. Sawyer, Antoinette Hollestelle, Olivia Fletcher, Robert Winqvist, Hermann Brenner, Arto Mannermaa, Ute Hamann, Alfons Meindl, Annika Lindblom, Wei Zheng, Peter Devillee, Mark S. Goldberg, Jan Lubinski, Vessela Kristensen, Anthony Swerdlow, Hoda Anton-Culver, Thilo Dörk, Kenneth Muir, Keitaro Matsuo, Anna H. Wu, Paolo Radice, Soo Hwang Teo, Xiao Ou Shu, William Blot, Daehee Kang, Mikael Hartman, Suleeporn Sangrajrang, Chen Yang Shen, Melissa C. Southey, Daniel J. Park, Fleur Hammet, Jennifer Stone, Laura J.Van T. Veer, Emiel J. Rutgers, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Julian Peto, Michael G. Schrauder, Arif B. Ekici, Matthias W. Beckmann, Isabel Dos Santos Silva, Nichola Johnson, Helen Warren, Ian Tomlinson, Michael J. Kerin, Nicola Miller, Federick Marme, Andreas Schneeweiss, Christof Sohn, Therese Truong, Pierre Laurent-Puig, Pierre Kerbrat, Børge G. Nordestgaard, Sune F. Nielsen, Henrik Flyger, Roger L. Milne, Jose Ignacio Arias Perez, Primitiva Menéndez, Heiko Müller, Volker Arndt, Christa Stegmaier, Peter Lichtner, Magdalena Lochmann, Christina Justenhoven, Yon Dschun Ko, Taru A. Muranen, Kristiina Aittomäki, Carl Blomqvist, Dario Greco, Tuomas Heikkinen, Hidemi Ito, Hiroji Iwata, Yasushi Yatabe, Natalia N. Antonenkova, Sara Margolin, Vesa Kataja, Veli Matti Kosma, Jaana M. Hartikainen, Rosemary Balleine, Chiu Chen Tseng, David Van Den Berg, Daniel O. Stram, Patrick Neven, Anne Sophie Dieudonné, Karin Leunen, Anja Rudolph, Stefan Nickels, Dieter Flesch-Janys, Paolo Peterlongo, Bernard Peissel, Loris Bernard, Janet E. Olson, Xianshu Wang, Kristen Stevens, Gianluca Severi, Laura Baglietto, Catriona McLean, Gerhard A. Coetzee, Ye Feng, Brian E. Henderson, Fredrick Schumacher, Natalia V. Bogdanova, France Labrèche, Martine Dumont, Cheng Har Yip, Nur Aishah Mohd Taib, Ching Yu Cheng, Martha Shrubsole, Jirong Long, Katri Pylkäs, Arja Jukkola-Vuorinen, Saila Kauppila, Julia A. Knight, Gord Glendon, Anna Marie Mulligan, Robertus A.E.M. Tollenaar, Caroline M. Seynaeve, Mieke Kriege, Maartje J. Hooning, Ans M.W. Van Den Ouweland, Carolien H.M. Van Deurzen, Wei Lu, Yu Tang Gao, Hui Cai, Sabapathy P. Balasubramanian, Simon S. Cross, Malcolm W.R. Reed, Lisa Signorello, Qiuyin Cai, Mitul Shah, Hui Miao, Ching Wan Chan, Kee Seng Chia, Anna Jakubowska, Katarzyna Jaworska, Katarzyna Durda, Chia Ni Hsiung, Pei Ei Wu, Jyh Cherng Yu, Alan Ashworth, Michael Jones, Daniel C. Tessier, Anna González-Neira, Guillermo Pita, M. Rosario Alonso, Daniel Vincent, Francois Bacot, Christine B. Ambrosone, Elisa V. Bandera, Esther M. John, Gary K. Chen, Jennifer J. Hu, Jorge L. Rodriguez-Gil, Leslie Bernstein, Michael F. Press, Regina G. Ziegler, Robert M. Millikan, Sandra L. Deming-Halverson, Sarah Nyante, Sue A. Ingles, Quinten Waisfisz, Helen Tsimiklis, Enes Makalic, Daniel Schmidt, Minh Bui, Lorna Gibson, Bertram Müller-Myhsok, Rita K. Schmutzler, Rebecca Hein, Norbert Dahmen, Lars Beckmann, Kirsimari Aaltonen, Kamila Czene, Astrid Irwanto, Jianjun Liu, Clare Turnbull, Nazneen Rahman, Hanne Meijers-Heijboer, Andre G. Uitterlinden, Fernando Rivadeneira, Curtis Olswold, Susan Slager, Robert Pilarski, Foluso Ademuyiwa, Irene Konstantopoulou, Nicholas G. Martin, Grant W. Montgomery, Dennis J. Slamon, Claudia Rauh, Michael P. Lux, Sebastian M. Jud, Thomas Bruning, Joellen Weaver, Priyanka Sharma, Harsh Pathak, Will Tapper, Sue Gerty, Lorraine Durcan, Dimitrios Trichopoulos, Rosario Tumino, Petra H. Peeters, Rudolf Kaaks, Daniele Campa, Federico Canzian, Elisabete Weiderpass, Mattias Johansson, Kay Tee Khaw, Ruth Travis, Françoise Clavel-Chapelon, Laurence N. Kolonel, Constance Chen, Andy Beck, Susan E. Hankinson, Christine D. Berg, Robert N. Hoover, Jolanta Lissowska, Jonine D. Figueroa, Daniel I. Chasman, Mia M. Gaudet, W. Ryan Diver, Walter C. Willett, David J. Hunter, Jacques Simard, Javier Benitez, Alison M. Dunning, Mark E. Sherman, Georgia Chenevix-Trench, Stephen J. Chanock, Per Hall, Paul D.P. Pharoah, Celine Vachon, Douglas F. Easton, Christopher A. Haiman, Peter Kraft

Research output: Contribution to journalArticlepeer-review

275 Scopus citations

Abstract

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10-12 and LGR6, P = 1.4 × 10-8), 2p24.1 (P = 4.6 × 10-8) and 16q12.2 (FTO, P = 4.0 × 10-8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

Original languageEnglish (US)
Pages (from-to)392-398
Number of pages7
JournalNature genetics
Volume45
Issue number4
DOIs
StatePublished - Apr 2013

ASJC Scopus subject areas

  • Genetics

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