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

Fergus J Couch ; Karoline B Kuchenbaecker ; Kyriaki Michailidou ; Gustavo A Mendoza-Fandino ; Silje Nord ; Janna Lilyquist ; Curtis Olswold ; Emily Hallberg ; Simona Agata ; Habibul Ahsan ; +239 more... Kristiina Aittomäki ; Christine Ambrosone ; Irene L Andrulis ; Hoda Anton-Culver ; Volker Arndt ; Banu K Arun ; Brita Arver ; Monica Barile ; Rosa B Barkardottir ; Daniel Barrowdale ; Lars Beckmann ; Matthias W Beckmann ; Javier Benitez ; Stephanie V Blank ; Carl Blomqvist ; Natalia V Bogdanova ; Stig E Bojesen ; Manjeet K Bolla ; Bernardo Bonanni ; Hiltrud Brauch ; Hermann Brenner ; Barbara Burwinkel ; Saundra S Buys ; Trinidad Caldes ; Maria A Caligo ; Federico Canzian ; Jane Carpenter ; Jenny Chang-Claude ; Stephen J Chanock ; Wendy K Chung ; Kathleen BM Claes ; Angela Cox ; Simon S Cross ; Julie M Cunningham ; Kamila Czene ; Mary B Daly ; Francesca Damiola ; Hatef Darabi ; Miguel de la Hoya ; Peter Devilee ; Orland Diez ; Yuan C Ding ; Riccardo Dolcetti ; Susan M Domchek ; Cecilia M Dorfling ; Isabel Dos-Santos-Silva

; Martine Dumont ; Alison M Dunning ; Diana M Eccles ; Hans Ehrencrona ; Arif B Ekici ; Heather Eliassen ; Steve Ellis ; Peter A Fasching ; Jonine Figueroa ; Dieter Flesch-Janys ; Asta Försti ; Florentia Fostira ; William D Foulkes ; Tara Friebel ; Eitan Friedman ; Debra Frost ; Marike Gabrielson ; Marilie D Gammon ; Patricia A Ganz ; Susan M Gapstur ; Judy Garber ; Mia M Gaudet ; Simon A Gayther ; Anne-Marie Gerdes ; Maya Ghoussaini ; Graham G Giles ; Gord Glendon ; Andrew K Godwin ; Mark S Goldberg ; David E Goldgar ; Anna González-Neira ; Mark H Greene ; Jacek Gronwald ; Pascal Guénel ; Marc Gunter ; Lothar Haeberle ; Christopher A Haiman ; Ute Hamann ; Thomas VO Hansen ; Steven Hart ; Sue Healey ; Tuomas Heikkinen ; Brian E Henderson ; Josef Herzog ; Frans BL Hogervorst ; Antoinette Hollestelle ; Maartje J Hooning ; Robert N Hoover ; John L Hopper ; Keith Humphreys ; David J Hunter ; Tomasz Huzarski ; Evgeny N Imyanitov ; Claudine Isaacs ; Anna Jakubowska ; Paul James ; Ramunas Janavicius ; Uffe Birk Jensen ; Esther M John ; Michael Jones ; Maria Kabisch ; Siddhartha Kar ; Beth Y Karlan ; Sofia Khan ; Kay-Tee Khaw ; Muhammad G Kibriya ; Julia A Knight ; Yon-Dschun Ko ; Irene Konstantopoulou ; Veli-Matti Kosma ; Vessela Kristensen ; Ava Kwong ; Yael Laitman ; Diether Lambrechts ; Conxi Lazaro ; Eunjung Lee ; Loic Le Marchand ; Jenny Lester ; Annika Lindblom ; Noralane Lindor ; Sara Lindstrom ; Jianjun Liu ; Jirong Long ; Jan Lubinski ; Phuong L Mai ; Enes Makalic ; Kathleen E Malone ; Arto Mannermaa ; Siranoush Manoukian ; Sara Margolin ; Frederik Marme ; John WM Martens ; Lesley McGuffog ; Alfons Meindl ; Austin Miller ; Roger L Milne ; Penelope Miron ; Marco Montagna ; Sylvie Mazoyer ; Anna M Mulligan ; Taru A Muranen ; Katherine L Nathanson ; Susan L Neuhausen ; Heli Nevanlinna ; Børge G Nordestgaard ; Robert L Nussbaum ; Kenneth Offit ; Edith Olah ; Olufunmilayo I Olopade ; Janet E Olson ; Ana Osorio ; Sue K Park ; Petra H Peeters ; Bernard Peissel ; Paolo Peterlongo ; Julian Peto

; Catherine M Phelan ; Robert Pilarski ; Bruce Poppe ; Katri Pylkäs ; Paolo Radice ; Nazneen Rahman ; Johanna Rantala ; Christine Rappaport ; Gad Rennert ; Andrea Richardson ; Mark Robson ; Isabelle Romieu ; Anja Rudolph ; Emiel J Rutgers ; Maria-Jose Sanchez ; Regina M Santella ; Elinor J Sawyer ; Daniel F Schmidt ; Marjanka K Schmidt ; Rita K Schmutzler ; Fredrick Schumacher ; Rodney Scott ; Leigha Senter ; Priyanka Sharma ; Jacques Simard ; Christian F Singer ; Olga M Sinilnikova ; Penny Soucy ; Melissa Southey ; Doris Steinemann ; Marie Stenmark-Askmalm ; Dominique Stoppa-Lyonnet ; Anthony Swerdlow ; Csilla I Szabo ; Rulla Tamimi ; William Tapper ; Manuel R Teixeira ; Soo-Hwang Teo ; Mary B Terry ; Mads Thomassen ; Deborah Thompson ; Laima Tihomirova ; Amanda E Toland ; Robert AEM Tollenaar ; Ian Tomlinson ; Thérèse Truong ; Helen Tsimiklis ; Alex Teulé ; Rosario Tumino ; Nadine Tung ; Clare Turnbull ; Giski Ursin ; Carolien HM van Deurzen ; Elizabeth J van Rensburg ; Raymonda Varon-Mateeva ; Zhaoming Wang ; Shan Wang-Gohrke ; Elisabete Weiderpass ; Jeffrey N Weitzel ; Alice Whittemore ; Hans Wildiers ; Robert Winqvist ; Xiaohong R Yang ; Drakoulis Yannoukakos ; Song Yao ; M Pilar Zamora ; Wei Zheng ; Per Hall ; Peter Kraft ; Celine Vachon ; Susan Slager ; Georgia Chenevix-Trench ; Paul DP Pharoah ; Alvaro AN Monteiro ; Montserrat García-Closas ; Douglas F Easton ; Antonis C Antoniou ; (2016) Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer. Nature communications, 7 (1). 11375-. ISSN 2041-1723 DOI: 10.1038/ncomms11375

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Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 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 ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.