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

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 ancestry1 . The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4 . 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.

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Item Type:	Article
Authors/Creators:	Garcia-Closas, M Couch, FJ Lindstrom, S Michailidouo, K Schmidt, MK Brook, MN Orr, N Rhie, SK Riboli, E Feigelson, HS Le Marchand, L Buring, JE Eccles, D Miron, P Fasching, PA Brauch, H Chang-Claude, J Carpenter, J Godwin, AK Nevanlinna, H Giles, GG Cox, A https://orcid.org/0000-0002-5138-1099 Hopper, JL Bolla, MK Wang, Q Dennis, J Dicks, E Howat, WJ Schoof, N Bojesen, SE Lambrechts, D Broeks, A Andrulis, IL Guenel, P Burwinkel, B Sawyer, EJ Hollestelle, A Fletcher, O Winqvist, R Brenner, H Mannermaa, A Hamann, U Meindl, A Lindblom, A Zheng, W Devillee, P Goldberg, MS Lubinski, J Kristensen, V Swerdlow, A Anton-Culver, H Doerk, T Muir, K Matsuo, K Wu, AH Radice, P Teo, SH Shu, X-O Blot, W Kang, D Hartman, M Sangrajrang, S Shen, C-Y Southey, MC Park, DJ Hammet, F Stone, J Van't Veer, LJ Rutgers, EJ Lophatananon, A Stewart-Brown, S Siriwanarangsan, P Peto, J Schrauder, MG Ekici, AB Beckmann, MW Silva, IDS Johnson, N Warren, H Tomlins, I Kerin, MJ Miller, N Marme, F Schneeweiss, A Sohn, C Truong, T Laurent-Puig, P Kerbrat, P Nordestgaard, BG Nielsen, SF Flyger, H Milne, RL Arias Perez, JI Menendez, P Mueller, H Arndt, V Stegmaier, C Lichtner, P Lochmann, M Justenhoven, C Ko, Y-D Muranen, TA Aittomaki, K Blomqvist, C Greco, D Heikkinen, T Ito, H Iwata, H Yatabe, Y Antonenkova, NN Margolin, S Kataja, V Kosma, V-M Hartikainen, JM Balleine, R Tseng, C-C Van den Berg, D Stram, DO Neven, P Dieudonne, A-S Leunen, K Rudolph, A Nickels, S Flesch-Janys, D Peterlongo, P Peissel, B Bernard, L Olson, JE Wang, X Stevens, K Severi, G Baglietto, L McLean, C Coetzee, GA Feng, Y Henderson, BE Schumacher, F Bogdanova, NV Labreche, F Dumont, M Yip, CH Taib, NAM Cheng, C-Y Shrubsole, M Long, J Pylkas, K Jukkola-Vuorinen, A Kauppila, S Knight, JA Glendon, G Mulligan, AM Tollenaar, RAEM Seynaeve, CM Kriege, M Hooning, MJ van den Ouweland, AMW van Deurzen, CHM Lu, W Gao, Y-T Cai, H Balasubramanian, SP https://orcid.org/0000-0001-5953-2843 Cross, SS https://orcid.org/0000-0003-2044-1754 Reed, MWR Signorello, L Cai, Q Shah, M Miao, H Chan, CW Chia, KS Jakubowska, A Jaworska, K Durda, K Hsiung, C-N Wu, P Yu, J-C Ashworth, A Jones, M Tessier, DC Gonzalez-Neira, A Pita, G Alonso, MR Vincent, D Bacot, F Ambrosone, CB Bandera, EV John, EM Chen, GK Hu, JJ Rodriguez-Gil, JL Bernstein, L Press, MF Ziegler, RG Millikan, RM Deming-Halverson, SL Nyante, S Ingles, SA Waisfisz, Q Tsimiklis, H Makalic, E Schmidt, D Bui, M Gibson, L Mueller-Myhsok, B Schmutzler, RK Hein, R Dahmen, N Beckmann, L Aaltonen, K Czene, K Irwanto, A Liu, J Turnbull, C Rahman, N Meijers-Heijboer, H Uitterlinden, AG Rivadeneira, F Olswold, C Slager, S Pilarski, R Ademuyiwa, F Konstantopoulou, I Martin, NG Montgomery, GW Slamon, DJ Rauh, C Lux, MP Jud, SM Bruning, T Weaver, J Harma, P Pathak, H Tapper, W Gerty, S Durcan, L Trichopoulos, D Tumino, R Peeters, PH Kaaks, R Campa, D Canzian, F Weiderpass, E Johansson, M Khaw, K-T Travis, R Clavel-Chapelon, F Kolonel, LN Chen, C Beck, A Hankinson, SE Berg, CD Hoover, RN Lissowska, J Figueroa, JD Chasman, DI Gaudet, MM Diver, WR Willett, WC Hunter, DJ Simard, J Benitez, J Dunning, AM Sherman, ME Chenevix-Trench, G Chanock, SJ Hall, P Pharoah, PDP Vachon, C Easton, DF Haiman, CA Kraft, P Breast, GEI Investigators, K FBCS, FBCS Bank, ABCT
Copyright, Publisher and Additional Information:	©2013 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: 27 March 2013 Published (online): 27 March 2013 Accepted: 29 January 2013
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) 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:	20 Jan 2017 15:33
Last Modified:	20 Jan 2017 15:33
Published Version:	https://doi.org/10.1038/ng.2561
Status:	Published
Publisher:	Nature Publishing Group
Refereed:	Yes
Identification Number:	10.1038/ng.2561
Related URLs:	Author
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:110837

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

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