Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
Authors: Couch Fergus J. , Kuchenbaecker Karoline B. , Michailidou Kyriaki , Mendoza-Fandino Gustavo A. , Nord Silje , Lilyquist Janna , Olswold Curtis , Hallberg Emily , Agata Simona , Ahsan Habibul , Aittomäki Kristiina , Ambrosone Christine , Andrulis Irene L. , Anton-Culver Hoda , Arndt Volker , Arun Banu K. , Arver Brita , Barile Monica , Barkardottir Rosa B. , Barrowdale Daniel , Beckmann Lars , Beckmann Matthias W. , Benitez Javier , Blank Stephanie V. , Blomqvist Carl , Bogdanova Natalia V. , Bojesen Stig E. , Bolla Manjeet K. , Bonanni Bernardo , Brauch Hiltrud , Brenner Hermann , Burwinkel Barbara , Buys Saundra S. , Caldes Trinidad , Caligo Maria A. , Canzian Federico , Carpenter Jane , Chang-Claude Jenny , Chanock Stephen J. , Chung Wendy K. , Claes Kathleen B. M. , Cox Angela , Cross Simon S. , Cunningham Julie M. , Czene Kamila , Daly Mary B. , Damiola Francesca , Darabi Hatef , de la Hoya Miguel , Devilee Peter , Diez Orland , Ding Yuan C. , Dolcetti Riccardo , Domchek Susan M. , Dorfling Cecilia M. , dos-Santos-Silva Isabel , Dumont Martine , Dunning Alison M. , Eccles Diana M. , Ehrencrona Hans , Ekici Arif B. , Eliassen Heather , Ellis Steve , Fasching Peter A. , Figueroa Jonine , Flesch-Janys Dieter , Försti Asta , Fostira Florentia , Foulkes William D. , Friebel Tara , Friedman Eitan , Frost Debra , Gabrielson Marike , Gammon Marilie D. , Ganz Patricia A. , Gapstur Susan M. , Garber Judy , Gaudet Mia M. , Gayther Simon A. , Gerdes Anne-Marie , Ghoussaini Maya , Giles Graham G. , Glendon Gord , Godwin Andrew K. , Goldberg Mark S. , Goldgar David E. , González-Neira Anna , Greene Mark H. , Gronwald Jacek , Guénel Pascal , Gunter Marc , Haeberle Lothar , Haiman Christopher A. , Hamann Ute , Hansen Thomas V. O. , Hart Steven , Healey Sue , Heikkinen Tuomas , Henderson Brian E. , Herzog Josef , Hogervorst Frans B. L. , Hollestelle Antoinette , Hooning Maartje J. , Hoover Robert N. , Hopper John L. , Humphreys Keith , Hunter David J. , Huzarski Tomasz , Imyanitov Evgeny N. , Isaacs Claudine , Jakubowska Anna , James Paul , Janavicius Ramunas , Jensen Uffe Birk , John Esther M. , Jones Michael , Kabisch Maria , Kar Siddhartha , Karlan Beth Y. , Khan Sofia , Khaw Kay-Tee , Kibriya Muhammad G. , Knight Julia A. , Ko Yon-Dschun , Konstantopoulou Irene , Kosma Veli-Matti , Kristensen Vessela , Kwong Ava , Laitman Yael , Lambrechts Diether , Lazaro Conxi , Lee Eunjung , Le Marchand Loic , Lester Jenny , Lindblom Annika , Lindor Noralane , Lindstrom Sara , Liu Jianjun , Long Jirong , Lubinski Jan , Mai Phuong L. , Makalic Enes , Malone Kathleen E. , Mannermaa Arto , Manoukian Siranoush , Margolin Sara , Marme Frederik , Martens John W. M. , McGuffog Lesley , Meindl Alfons , Miller Austin , Milne Roger L. , Miron Penelope , Montagna Marco , Mazoyer Sylvie , Mulligan Anna M. , Muranen Taru A. , Nathanson Katherine L. , Neuhausen Susan L. , Nevanlinna Heli , Nordestgaard Børge G. , Nussbaum Robert L. , Offit Kenneth , Olah Edith , Olopade Olufunmilayo I. , Olson Janet E. , Osorio Ana , Park Sue K. , Peeters Petra H. , Peissel Bernard , Peterlongo Paolo , Peto Julian , Phelan Catherine M. , Pilarski Robert , Poppe Bruce , Pylkäs Katri , Radice Paolo , Rahman Nazneen , Rantala Johanna , Rappaport Christine , Rennert Gad , Richardson Andrea , Robson Mark , Romieu Isabelle , Rudolph Anja , Rutgers Emiel J. , Sanchez Maria-Jose , Santella Regina M. , Sawyer Elinor J. , Schmidt Daniel F. , Schmidt Marjanka K. , Schmutzler Rita K. , Schumacher Fredrick , Scott Rodney , Senter Leigha , Sharma Priyanka , Simard Jacques , Singer Christian F. , Sinilnikova Olga M. , Soucy Penny , Southey Melissa , Steinemann Doris , Stenmark-Askmalm Marie , Stoppa-Lyonnet Dominique , Swerdlow Anthony , Szabo Csilla I. , Tamimi Rulla , Tapper William , Teixeira Manuel R. , Teo Soo-Hwang , Terry Mary B. , Thomassen Mads , Thompson Deborah , Tihomirova Laima , Toland Amanda E. , Tollenaar Robert A. E. M. , Tomlinson Ian , Truong Thérèse , Tsimiklis Helen , Teulé Alex , Tumino Rosario , Tung Nadine , Turnbull Clare , Ursin Giski , van Deurzen Carolien H. M. , van Rensburg Elizabeth J. , Varon-Mateeva Raymonda , Wang Zhaoming , Wang-Gohrke Shan , Weiderpass Elisabete , Weitzel Jeffrey N. , Whittemore Alice , Wildiers Hans , Winqvist Robert , Yang Xiaohong R. , Yannoukakos Drakoulis , Yao Song , Zamora M Pilar , Zheng Wei , Hall Per , Kraft Peter , Vachon Celine , Slager Susan , Chenevix-Trench Georgia , Pharoah Paul D. P. , Monteiro Alvaro A. N. , García-Closas Montserrat , Easton Douglas F. , Antoniou Antonis C. 
Published: April 2016

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.