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

Maya Ghoussaini, Olivia Fletcher, Kyriaki Michailidou, Clare Turnbull, Marjanka K. Schmidt, Ed Dicks, Joe Dennis, Qin Wang, Manjeet K. Humphreys, Craig Luccarini, Caroline Baynes, Don Conroy, Melanie Maranian, Shahana Ahmed, Kristy Driver, Nichola Johnson, Nicholas Orr, Isabel Dos Santos Silva, Quinten Waisfisz, Hanne Meijers-HeijboerAndre G. Uitterlinden, Fernando Rivadeneira, Per Hall, Kamila Czene, Astrid Irwanto, Jianjun Liu, Heli Nevanlinna, Kristiina Aittom Currency Signki, Carl Blomqvist, Alfons Meindl, Rita K. Schmutzler, Bertram Müller-Myhsok, Peter Lichtner, Jenny Chang-Claude, Rebecca Hein, Stefan Nickels, Dieter Flesch-Janys, Helen Tsimiklis, Enes Makalic, Daniel Schmidt, Minh Bui, John L. Hopper, Carmel Apicella, Daniel J. Park, Melissa Southey, David J. Hunter, Stephen J. Chanock, Annegien Broeks, Senno Verhoef, Frans B.L. Hogervorst, Peter A. Fasching, Michael P. Lux, Matthias W. Beckmann, Arif B. Ekici, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, Pascal Guénel, Thér̈se Truong, Emilie Cordina-Duverger, Florence Menegaux, Stig E. Bojesen, B̧rge G. Nordestgaard, Sune F. Nielsen, Henrik Flyger, Roger L. Milne, M. Rosario Alonso, Anna Gonzlez-Neira, Javier Ben-tez, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, Christina Clarke Dur, Hermann Brenner, Heiko Müller, Volker Arndt, Christa Stegmaier, Christina Justenhoven, Hiltrud Brauch, Thomas Brüning, Wang Gohrke Shan, Ursula Eilber, Thilo Dörk, Peter Schürmann, Michael Bremer, Peter Hillemanns, Natalia V. Bogdanova, Natalia N. Antonenkova, Yuri I. Rogov, Johann H. Karstens, Marina Bermisheva, Darya Prokofieva, Elza Khusnutdinova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli Matti Kosma, Jaana M. Hartikainen, Diether Lambrechts, Betul T. Yesilyurt, Giuseppe Floris, Karin Leunen, Siranoush Manoukian, Bernardo Bonanni, Stefano Fortuzzi, Paolo Peterlongo, Fergus J. Couch, Xianshu Wang, Kristen Stevens, Adam Lee, Graham G. Giles, Laura Baglietto, Gianluca Severi, Catriona McLean, Grethe Grenaker Alnæs, Vessela Kristensen, Anne Lise Bcrrensen-Dale, Esther M. John, Alexander Miron, Robert Winqvist, Katri Pylk Currency Signs, Arja Jukkola-Vuorinen, Saila Kauppila, Irene L. Andrulis, Gord Glendon, Anna Marie Mulligan, Peter Devilee, Christie J. Van Asperen, Rob A.E.M. Tollenaar, Caroline Seynaeve, Jonine D. Figueroa, Montserrat Garcia-Closas, Louise Brinton, Jolanta Lissowska, Maartje J. Hooning, Antoinette Hollestelle, Rogier A. Oldenburg, Ans M.W. Van Den Ouweland, Angela Cox, Malcolm W.R. Reed, Mitul Shah, Ania Jakubowska, Lubinski Jan, Katarzyna Jaworska, Katarzyna Durda, Michael Jones, Minouk Schoemaker, Alan Ashworth, Anthony Swerdlow, Jonathan Beesley, Xiaoqing Chen, Kenneth R. Muir, Artitaya Lophatananon, Suthee Rattanamongkongul, Arkom Chaiwerawattana, Daehee Kang, Keun Young Yoo, Dong Young Noh, Chen Yang Shen, Jyh Cherng Yu, Pei Ei Wu, Chia Ni Hsiung, Annie Perkins, Ruth Swann, Louiza Velentzis, Diana M. Eccles, Will J. Tapper, Susan M. Gerty, Nikki J. Graham, Bruce A.J. Ponder, Georgia Chenevix-Trench, Paul D.P. Pharoah, Mark Lathrop, Alison M. Dunning, Nazneen Rahman, Julian Peto, Douglas F. Easton

Research output: Contribution to journalArticle

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Abstract

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for g1/48% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in g1/470,000 cases and ĝ̂1/468,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 - 10 g35), 12q24 (rs1292011; P = 4.3 - 10 g19) and 21q21 (rs2823093; P = 1.1 - 10 g12). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.

Original languageEnglish (US)
Pages (from-to)312-318
Number of pages7
JournalNature Genetics
Volume44
Issue number3
DOIs
StatePublished - Mar 2012

ASJC Scopus subject areas

  • Genetics

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    Ghoussaini, M., Fletcher, O., Michailidou, K., Turnbull, C., Schmidt, M. K., Dicks, E., Dennis, J., Wang, Q., Humphreys, M. K., Luccarini, C., Baynes, C., Conroy, D., Maranian, M., Ahmed, S., Driver, K., Johnson, N., Orr, N., Dos Santos Silva, I., Waisfisz, Q., ... Easton, D. F. (2012). Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nature Genetics, 44(3), 312-318. https://doi.org/10.1038/ng.1049