Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

FJ Couch, KB Kuchenbaecker, K Michailidou, GA Mendoza-Fandino, S Nord, J Lilyquist, C Olswold, E Hallberg, S Agata, H Ahsan, K Aittomaki, C Ambrosone, IL Andrulis, H Anton-Culver, V Arndt, BK Arun, B Arver, M Barile, RB Barkardottir, D BarrowdaleL Beckmann, MW Beckmann, J Benitez, SV Blank, C Blomqvist, NV Bogdanova, SE Bojesen, MK Bolla, B Bonanni, H Brauch, H Brenner, B Burwinkel, SS Buys, T Caldes, MA Caligo, F Canzian, J Carpenter, J Chang-Claude, SJ Chanock, WK Chung, KBM Claes, A Cox, SS Cross, JM Cunningham, K Czene, MB Daly, F Damiola, H Darabi, M de la Hoya, P Devilee, O Diez, YC Ding, R Dolcetti, SM Domchek, CM Dorfling, I dos-Santos-Silva, M Dumont, AM Dunning, DM Eccles, H Ehrencrona, AB Ekici, H Eliassen, S Ellis, PA Fasching, J Figueroa, D Flesch-Janys, A Forsti, F Fostira, WD Foulkes, T Friebel, E Friedman, D Frost, M Gabrielson, MD Gammon, PA Ganz, SM Gapstur, J Garber, MM Gaudet, SA Gayther, AM Gerdes, M Ghoussaini, GG Giles, G Glendon, AK Godwin, MS Goldberg, DE Goldgar, A Gonzalez-Neira, MH Greene, J Gronwald, P Guenel, M Gunter, L Haeberle, CA Haiman, U Hamann, TVO Hansen, S Hart, S Healey, T Heikkinen, BE Henderson, J Herzog, FBL Hogervorst, Antoinette Hollestelle, Maartje Hooning, RN Hoover, JL Hopper, K Humphreys, DJ Hunter, T Huzarski, EN Imyanitov, C Isaacs, A Jakubowska, P James, R Janavicius, UB Jensen, EM John, M Jones, M Kabisch, S Kar, BY Karlan, Salima Khan, KT Khaw, MG Kibriya, JA Knight, YD Ko, I Konstantopoulou, VM Kosma, V Kristensen, A Kwong, Y Laitman, D Lambrechts, C (Conxi) Lazaro, E Lee, L Le Marchand, J Lester, A Lindblom, N Lindor, S Lindstrom, J (Jingjing) Liu, J Long, J Lubinski, PL Mai, E Makalic, KE Malone, A Mannermaa, S Manoukian, S Margolin, F Marme, John Martens, L McGuffog, A Meindl, A Miller, RL Milne, P Miron, M Montagna, S Mazoyer, AM Mulligan, TA Muranen, KL Nathanson, SL Neuhausen, H Nevanlinna, BG Nordestgaard, RL Nussbaum, K Offit, E Olah, OI Olopade, JE Olson, A Osorio, SK Park, PH Peeters, B Peissel, P Peterlongo, J Peto, CM Phelan, R Pilarski, B (Bruce) Poppe, K Pylkas, P Radice, N Rahman, J Rantala, C Rappaport, G Rennert, A Richardson, M Robson, I Romieu, A Rudolph, EJ Rutgers, MJ (Maria-Jose) Sanchez, RM Santella, EJ Sawyer, DF Schmidt, MK (Marjanka) Schmidt, RK Schmutzler, F Schumacher, R Scott, L Senter, P Sharma, J Simard, CF Singer, OM Sinilnikova, P Soucy, M Southey, D Steinemann, M Stenmark-Askmalm, D Stoppa-Lyonnet, A Swerdlow, CI Szabo, R Tamimi, W Tapper, MR Teixeira, SH Teo, MB Terry, M Thomassen, D Thompson, L Tihomirova, AE Toland, RAEM Tollenaar, I Tomlinson, T Truong, H Tsimiklis, A Teule, R Tumino, N Tung, C Turnbull, G Ursin, Carolien van Deurzen, EJ van Rensburg, R Varon-Mateeva, ZM Wang, S Wang-Gohrke, E Weiderpass, JN Weitzel, A Whittemore, H Wildiers, R Winqvist, XHR Yang, D Yannoukakos, S Yao, MP Zamora, W Zheng, P Hall, P Kraft, C Vachon, S Slager, G Chenevix-Trench, PDP Pharoah, AAN Monteiro, M Garcia-Closas, DF Easton, AC Antoniou

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Abstract

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
Original languageUndefined/Unknown
Article number11375
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 2016

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