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

Abstract

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ∼70,000 cases and ∼68,000 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(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). 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.

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Item Type:	Article
Authors/Creators:	Ghoussaini, M Fletcher, O Michailidou, K Turnbull, C Schmidt, MK Dicks, E Dennis, J Wang, Q Humphreys, MK Luccarini, C Baynes, C Conroy, D Maranian, M Ahmed, S Driver, K Johnson, N Orr, N Silva, IDS Waisfisz, Q Meijers-Heijboer, H Uitterlinden, AG Rivadeneira, F Hall, P Czene, K Irwanto, A Liu, J Nevanlinna, H Aittomaki, K Blomqvist, C Meindl, A Schmutzler, RK Mueller-Myhsok, B Lichtner, P Chang-Claude, J Hein, R Nickels, S Flesch-Janys, D Tsimiklis, H Makalic, E Schmidt, D Bui, M Hopper, JL Apicella, C Park, DJ Southey, M Hunter, DJ Chanock, SJ Broeks, A Verhoef, S Hogervorst, FBL Fasching, PA Lux, MP Beckmann, MW Ekici, AB Sawyer, E Tomlinson, I Kerin, M Marme, F Schneeweiss, A Sohn, C Burwinkel, B Guenel, P Truong, T Cordina-Duverger, E Menegaux, F Bojesen, SE Nordestgaard, BG Nielsen, SF Flyger, H Milne, RL Rosario Alonso, M Gonzalez-Neira, A Benitez, J Anton-Culver, H Ziogas, A Bernstein, L Dur, CC Brenner, H Mueller, H Arndt, V Stegmaier, C Justenhoven, C Brauch, H Bruening, T Wang-Gohrke, S Eilber, U Doerk, T Schuermann, P Bremer, M Hillemanns, P Bogdanova, NV Antonenkova, NN Rogov, YI Karstens, JH Bermisheva, M Prokofieva, D Khusnutdinova, E Lindblom, A Margolin, S Mannermaa, A Kataja, V Kosma, V-M Hartikainen, JM Lambrechts, D Yesilyurt, BT Floris, G Leunen, K Manoukian, S Bonanni, B Fortuzzi, S Peterlongo, P Couch, FJ Wang, X Stevens, K Lee, A Giles, GG Baglietto, L Severi, G McLean, C Alnaes, GG Kristensen, V Borrensen-Dale, A-L John, EM Miron, A Winqvist, R Pylkas, K Jukkola-Vuorinen, A Kauppila, S Andrulis, IL Glendon, G Mulligan, AM Devilee, P van Asperen, CJ Tollenaar, RAEM Seynaeve, C Figueroa, JD Garcia-Closas, M Brinton, L Lissowska, J Hooning, MJ Hollestelle, A Oldenburg, RA van den Ouweland, AMW Cox, A https://orcid.org/0000-0002-5138-1099 Reed, MWR Shah, M Jakubowska, A Lubinski, J Jaworska, K Durda, K Jones, M Schoemaker, M Ashworth, A Swerdlow, A Beesley, J Chen, X Muir, KR Lophatananon, A Rattanamongkongul, S Chaiwerawattana, A Kang, D Yoo, K-Y Noh, D-Y Shen, C-Y Yu, J-C Wu, P-E Hsiung, C-N Perkins, A Swann, R Velentzis, L Eccles, DM Tapper, WJ Gerty, SM Graham, NJ Ponder, BAJ Chenevix-Trench, G Pharoah, PDP Lathrop, M Dunning, AM Rahman, N Peto, J Easton, DF Here, NCG FBCS Gene, EIBC Investigators, K Grp, AOCS
Copyright, Publisher and Additional Information:	© 2014 Nature Publishing Group. This is an author produced version of a paper subsequently published in Nature Genetics. Uploaded in accordance with the publisher's self-archiving policy.
Dates:	Published: March 2012
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals
Depositing User:	Symplectic Sheffield
Date Deposited:	09 Dec 2016 16:42
Last Modified:	21 Mar 2018 11:32
Published Version:	https://doi.org/10.1038/ng.1049
Status:	Published
Publisher:	Nature Publishing Group
Refereed:	Yes
Identification Number:	10.1038/ng.1049
Related URLs:	Author
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:107841

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

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