Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Roger L. Milne; Karoline B. Kuchenbaecker; Kyriaki Michailidou; Jonathan Beesley; Siddhartha Kar; Sara Lindström; Shirley Hui; Audrey Lemaçon; Penny Soucy; Joe Dennis; Xia Jiang; Asha Rostamianfar; Hilary Finucane; Manjeet K. Bolla; Lesley McGuffog; Qin Wang; Cora M. Aalfs; Investigators Abctctb; Marcia Adams; Julian Adlard; Simona Agata; Shahana Ahmed; Habibul Ahsan; Kristiina Äki Aittom; Al Ejeh Fares; Jamie Allen; Christine B. Ambrosone; Christopher I. Amos; Irene L. Andrulis; Hoda Anton-Culver; Natalia N. Antonenkova; Volker Arndt; Norbert Arnold; Kristan J. Aronson; Bernd Auber; Paul L. Auer; Margreet G.M. Ausems; Jacopo Azzollini; Bacot François; Judith Nã Balma; Monica Barile; Laure Barjhoux; Rosa B. Barkardottir; Myrto Barrdahl; Daniel Barnes; Daniel Barrowdale; Caroline Baynes; Matthias W. Beckmann; Javier Benitez; Marina Bermisheva; Leslie Bernstein; Yves Jean Bignon; Kathleen R. Blazer; Marinus J. Blok; Carl Blomqvist; William Blot; Kristie Bobolis; Bram Boeckx; Natalia V. Bogdanova; Anders Bojesen; Stig E. Bojesen; Bernardo Bonanni; Børresen Dale Anne-Lise; Aniko Bozsik; Angela R. Bradbury; Judith S. Brand; Hiltrud Brauch; Hermann Brenner; Bressac De Paillerets Brigitte; Carole Brewer; Louise Brinton; Per Broberg; Brooks Wilson Angela; Joan Brunet; Thomas Brüning; Barbara Burwinkel; Saundra S. Buys; Jinyoung Byun; Qiuyin Cai; Trinidad És Cald; Maria A. Caligo; Ian Campbell; Federico Canzian; Olivier Caron; Angel Carracedo; Brian D. Carter; Castelao Esteban; Laurent Castera; Caux Moncoutier Virginie; Salina B. Chan; Chang Claude Jenny; Stephen J. Chanock; Xiaoqing Chen; Ting Yuan David Cheng; Jocelyne Chiquette; Hans Christiansen; Kathleen B. Claes; Christine L. Clarke; Thomas Conner; Don M. Conroy; Jackie Cook; Emilie Cordina-Duverger; Sten Cornelissen; Isabelle Coupier; Angela Cox; David G. Cox; Simon S. Cross; Katarina Cuk; Julie M. Cunningham; Kamila Czene; Mary B. Daly; Francesca Damiola; Hatef Darabi; Rosemarie Davidson; Kim De L. Leeneer; Peter Devilee; Ed Dicks; Orland Diez; Yuan Chun Ding; Nina Ditsch; Kimberly F. Doheny; Susan M. Domchek; Cecilia M. Dorfling; Thilo Dörk; Isabel Dos-Santos-Silva; Stéphane Dubois; Pierre Antoine Dugué; Martine Dumont; Alison M. Dunning; Lorraine Durcan; Miriam Dwek; Bernd Dworniczak; Diana Eccles; Ros Eeles; Hans Ehrencrona; Ursula Eilber; Bent Ejlertsen; Arif B. Ekici; A. Heather Eliassen; Christoph Engel; Mikael Eriksson; Laura Fachal; Laurence Faivre; Peter A. Fasching; Ulrike Faust; Jonine Figueroa; Dieter Flesch-Janys; Olivia Fletcher; Henrik Flyger; William D. Foulkes; Eitan Friedman; Lin Fritschi; Debra Frost; Marike Gabrielson; Pragna Gaddam; Marilie D. Gammon; Patricia A. Ganz; Susan M. Gapstur; Judy Garber; Vanesa Garcia-Barberan; José A. Garciá-Saénz; Mia M. Gaudet; Marion Gauthier-Villars; Andrea Gehrig; Vassilios Georgoulias; Anne Marie Gerdes; Graham G. Giles; Gord Glendon; Andrew K. Godwin; Mark S. Goldberg; David E. Goldgar; Anna González-Neira; Paul Goodfellow; Mark H. Greene; Grethe Alnæs I. Grenaker; Mervi Grip; Jacek Gronwald; Anne Grundy; Daphne Kaulich Gschwantler; Pascal Guénel; Qi Guo; Lothar Haeberle; Eric Hahnen; Christopher A. Haiman; Niclas Håkansson; Emily Hallberg; Ute Hamann; Nathalie Hamel; Susan Hankinson; Thomas V. Hansen; Patricia Harrington; Steven N. Hart; Jaana M. Hartikainen; Catherine S. Healey; Alexander Hein; Sonja Helbig; Alex Henderson; Jane Heyworth; Belynda Hicks; Peter Hillemanns; Shirley Hodgson; Frans B. Hogervorst; Antoinette Hollestelle; Maartje J. Hooning; Bob Hoover; John L. Hopper; Chunling Hu; Guanmengqian Huang; Peter J. Hulick; Keith Humphreys; David J. Hunter; Evgeny N. Imyanitov; Claudine Isaacs; Motoki Iwasaki; Louise Izatt; Anna Jakubowska; Paul James; Ramunas Janavicius; Wolfgang Janni; Uffe Birk Jensen; Esther M. John; Nichola Johnson; Kristine Jones; Michael Jones; Arja Jukkola-Vuorinen; Rudolf Kaaks; Maria Kabisch; Katarzyna Kaczmarek; Daehee Kang; Karin Kast; Renske Keeman; Michael J. Kerin; Carolien M. Kets; Mac Hteld Keupers; Sofia Khan; Elza Khusnutdinova; Johanna I. Kiiski; Sung Won Kim; Julia A. Knight; Irene Konstantopoulou; Veli Matti Kosma; Vessela N. Kristensen; Torben A. Kruse; Ava Kwong; Anne Vibeke Lænkholm; Yael Laitman; Fiona Lalloo; Diether Lambrechts; Rachel Lloyd; Jennifer Stone

doi:10.1038/ng.3785

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Roger L. Milne, Karoline B. Kuchenbaecker, Kyriaki Michailidou, Jonathan Beesley, Siddhartha Kar, Sara Lindström, Shirley Hui, Audrey Lemaçon, Penny Soucy, Joe Dennis, Xia Jiang, Asha Rostamianfar, Hilary Finucane, Manjeet K. Bolla, Lesley McGuffog, Qin Wang, Cora M. Aalfs, Investigators Abctctb, Marcia Adams, Julian AdlardSimona Agata, Shahana Ahmed, Habibul Ahsan, Kristiina Äki Aittom, Al Ejeh Fares, Jamie Allen, Christine B. Ambrosone, Christopher I. Amos, Irene L. Andrulis, Hoda Anton-Culver, Natalia N. Antonenkova, Volker Arndt, Norbert Arnold, Kristan J. Aronson, Bernd Auber, Paul L. Auer, Margreet G.M. Ausems, Jacopo Azzollini, Bacot François, Judith Nã Balma, Monica Barile, Laure Barjhoux, Rosa B. Barkardottir, Myrto Barrdahl, Daniel Barnes, Daniel Barrowdale, Caroline Baynes, Matthias W. Beckmann, Javier Benitez, Marina Bermisheva, Leslie Bernstein, Yves Jean Bignon, Kathleen R. Blazer, Marinus J. Blok, Carl Blomqvist, William Blot, Kristie Bobolis, Bram Boeckx, Natalia V. Bogdanova, Anders Bojesen, Stig E. Bojesen, Bernardo Bonanni, Børresen Dale Anne-Lise, Aniko Bozsik, Angela R. Bradbury, Judith S. Brand, Hiltrud Brauch, Hermann Brenner, Bressac De Paillerets Brigitte, Carole Brewer, Louise Brinton, Per Broberg, Brooks Wilson Angela, Joan Brunet, Thomas Brüning, Barbara Burwinkel, Saundra S. Buys, Jinyoung Byun, Qiuyin Cai, Trinidad És Cald, Maria A. Caligo, Ian Campbell, Federico Canzian, Olivier Caron, Angel Carracedo, Brian D. Carter, Castelao Esteban, Laurent Castera, Caux Moncoutier Virginie, Salina B. Chan, Chang Claude Jenny, Stephen J. Chanock, Xiaoqing Chen, Ting Yuan David Cheng, Jocelyne Chiquette, Hans Christiansen, Kathleen B. Claes, Christine L. Clarke, Thomas Conner, Don M. Conroy, Jackie Cook, Emilie Cordina-Duverger, Sten Cornelissen, Isabelle Coupier, Angela Cox, David G. Cox, Simon S. Cross, Katarina Cuk, Julie M. Cunningham, Kamila Czene, Mary B. Daly, Francesca Damiola, Hatef Darabi, Rosemarie Davidson, Kim De L. Leeneer, Peter Devilee, Ed Dicks, Orland Diez, Yuan Chun Ding, Nina Ditsch, Kimberly F. Doheny, Susan M. Domchek, Cecilia M. Dorfling, Thilo Dörk, Isabel Dos-Santos-Silva, Stéphane Dubois, Pierre Antoine Dugué, Martine Dumont, Alison M. Dunning, Lorraine Durcan, Miriam Dwek, Bernd Dworniczak, Diana Eccles, Ros Eeles, Hans Ehrencrona, Ursula Eilber, Bent Ejlertsen, Arif B. Ekici, A. Heather Eliassen, Christoph Engel, Mikael Eriksson, Laura Fachal, Laurence Faivre, Peter A. Fasching, Ulrike Faust, Jonine Figueroa, Dieter Flesch-Janys, Olivia Fletcher, Henrik Flyger, William D. Foulkes, Eitan Friedman, Lin Fritschi, Debra Frost, Marike Gabrielson, Pragna Gaddam, Marilie D. Gammon, Patricia A. Ganz, Susan M. Gapstur, Judy Garber, Vanesa Garcia-Barberan, José A. Garciá-Saénz, Mia M. Gaudet, Marion Gauthier-Villars, Andrea Gehrig, Vassilios Georgoulias, Anne Marie Gerdes, Graham G. Giles, Gord Glendon, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Anna González-Neira, Paul Goodfellow, Mark H. Greene, Grethe Alnæs I. Grenaker, Mervi Grip, Jacek Gronwald, Anne Grundy, Daphne Kaulich Gschwantler, Pascal Guénel, Qi Guo, Lothar Haeberle, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Emily Hallberg, Ute Hamann, Nathalie Hamel, Susan Hankinson, Thomas V. Hansen, Patricia Harrington, Steven N. Hart, Jaana M. Hartikainen, Catherine S. Healey, Alexander Hein, Sonja Helbig, Alex Henderson, Jane Heyworth, Belynda Hicks, Peter Hillemanns, Shirley Hodgson, Frans B. Hogervorst, Antoinette Hollestelle, Maartje J. Hooning, Bob Hoover, John L. Hopper, Chunling Hu, Guanmengqian Huang, Peter J. Hulick, Keith Humphreys, David J. Hunter, Evgeny N. Imyanitov, Claudine Isaacs, Motoki Iwasaki, Louise Izatt, Anna Jakubowska, Paul James, Ramunas Janavicius, Wolfgang Janni, Uffe Birk Jensen, Esther M. John, Nichola Johnson, Kristine Jones, Michael Jones, Arja Jukkola-Vuorinen, Rudolf Kaaks, Maria Kabisch, Katarzyna Kaczmarek, Daehee Kang, Karin Kast, Renske Keeman, Michael J. Kerin, Carolien M. Kets, Mac Hteld Keupers, Sofia Khan, Elza Khusnutdinova, Johanna I. Kiiski, Sung Won Kim, Julia A. Knight, Irene Konstantopoulou, Veli Matti Kosma, Vessela N. Kristensen, Torben A. Kruse, Ava Kwong, Anne Vibeke Lænkholm, Yael Laitman, Fiona Lalloo, Diether Lambrechts, Rachel Lloyd, Jennifer Stone

School of Population and Global Health

Research output: Contribution to journal › Article › peer-review

271 Citations (Scopus)

Abstract

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10^-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

Original language	English
Pages (from-to)	1767-1778
Number of pages	12
Journal	Nature Genetics
Volume	49
Issue number	12
DOIs	https://doi.org/10.1038/ng.3785
Publication status	Published - 1 Dec 2017

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Access to Document

10.1038/ng.3785

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808456/

Cite this

Milne, R. L., Kuchenbaecker, K. B., Michailidou, K., Beesley, J., Kar, S., Lindström, S., Hui, S., Lemaçon, A., Soucy, P., Dennis, J., Jiang, X., Rostamianfar, A., Finucane, H., Bolla, M. K., McGuffog, L., Wang, Q., Aalfs, C. M., Abctctb, I., Adams, M., ... Stone, J. (2017). Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nature Genetics, 49(12), 1767-1778. https://doi.org/10.1038/ng.3785

@article{1882a58f246446ca90b2dbb2ffcd0e9a,

title = "Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer",

abstract = "Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.",

author = "Milne, {Roger L.} and Kuchenbaecker, {Karoline B.} and Kyriaki Michailidou and Jonathan Beesley and Siddhartha Kar and Sara Lindstr{\"o}m and Shirley Hui and Audrey Lema{\c c}on and Penny Soucy and Joe Dennis and Xia Jiang and Asha Rostamianfar and Hilary Finucane and Bolla, {Manjeet K.} and Lesley McGuffog and Qin Wang and Aalfs, {Cora M.} and Investigators Abctctb and Marcia Adams and Julian Adlard and Simona Agata and Shahana Ahmed and Habibul Ahsan and Aittom, {Kristiina {\"A}ki} and Fares, {Al Ejeh} and Jamie Allen and Ambrosone, {Christine B.} and Amos, {Christopher I.} and Andrulis, {Irene L.} and Hoda Anton-Culver and Antonenkova, {Natalia N.} and Volker Arndt and Norbert Arnold and Aronson, {Kristan J.} and Bernd Auber and Auer, {Paul L.} and Ausems, {Margreet G.M.} and Jacopo Azzollini and Bacot Fran{\c c}ois and Balma, {Judith N{\~a}} and Monica Barile and Laure Barjhoux and Barkardottir, {Rosa B.} and Myrto Barrdahl and Daniel Barnes and Daniel Barrowdale and Caroline Baynes and Beckmann, {Matthias W.} and Javier Benitez and Marina Bermisheva and Leslie Bernstein and Bignon, {Yves Jean} and Blazer, {Kathleen R.} and Blok, {Marinus J.} and Carl Blomqvist and William Blot and Kristie Bobolis and Bram Boeckx and Bogdanova, {Natalia V.} and Anders Bojesen and Bojesen, {Stig E.} and Bernardo Bonanni and Anne-Lise, {B{\o}rresen Dale} and Aniko Bozsik and Bradbury, {Angela R.} and Brand, {Judith S.} and Hiltrud Brauch and Hermann Brenner and Brigitte, {Bressac De Paillerets} and Carole Brewer and Louise Brinton and Per Broberg and Angela, {Brooks Wilson} and Joan Brunet and Thomas Br{\"u}ning and Barbara Burwinkel and Buys, {Saundra S.} and Jinyoung Byun and Qiuyin Cai and Cald, {Trinidad {\'E}s} and Caligo, {Maria A.} and Ian Campbell and Federico Canzian and Olivier Caron and Angel Carracedo and Carter, {Brian D.} and Castelao Esteban and Laurent Castera and Virginie, {Caux Moncoutier} and Chan, {Salina B.} and Jenny, {Chang Claude} and Chanock, {Stephen J.} and Xiaoqing Chen and Cheng, {Ting Yuan David} and Jocelyne Chiquette and Hans Christiansen and Claes, {Kathleen B.} and Clarke, {Christine L.} and Thomas Conner and Conroy, {Don M.} and Jackie Cook and Emilie Cordina-Duverger and Sten Cornelissen and Isabelle Coupier and Angela Cox and Cox, {David G.} and Cross, {Simon S.} and Katarina Cuk and Cunningham, {Julie M.} and Kamila Czene and Daly, {Mary B.} and Francesca Damiola and Hatef Darabi and Rosemarie Davidson and Leeneer, {Kim De L.} and Peter Devilee and Ed Dicks and Orland Diez and Ding, {Yuan Chun} and Nina Ditsch and Doheny, {Kimberly F.} and Domchek, {Susan M.} and Dorfling, {Cecilia M.} and Thilo D{\"o}rk and Isabel Dos-Santos-Silva and St{\'e}phane Dubois and Dugu{\'e}, {Pierre Antoine} and Martine Dumont and Dunning, {Alison M.} and Lorraine Durcan and Miriam Dwek and Bernd Dworniczak and Diana Eccles and Ros Eeles and Hans Ehrencrona and Ursula Eilber and Bent Ejlertsen and Ekici, {Arif B.} and Eliassen, {A. Heather} and Christoph Engel and Mikael Eriksson and Laura Fachal and Laurence Faivre and Fasching, {Peter A.} and Ulrike Faust and Jonine Figueroa and Dieter Flesch-Janys and Olivia Fletcher and Henrik Flyger and Foulkes, {William D.} and Eitan Friedman and Lin Fritschi and Debra Frost and Marike Gabrielson and Pragna Gaddam and Gammon, {Marilie D.} and Ganz, {Patricia A.} and Gapstur, {Susan M.} and Judy Garber and Vanesa Garcia-Barberan and Garci{\'a}-Sa{\'e}nz, {Jos{\'e} A.} and Gaudet, {Mia M.} and Marion Gauthier-Villars and Andrea Gehrig and Vassilios Georgoulias and Gerdes, {Anne Marie} and Giles, {Graham G.} and Gord Glendon and Godwin, {Andrew K.} and Goldberg, {Mark S.} and Goldgar, {David E.} and Anna Gonz{\'a}lez-Neira and Paul Goodfellow and Greene, {Mark H.} and Grenaker, {Grethe Aln{\ae}s I.} and Mervi Grip and Jacek Gronwald and Anne Grundy and Gschwantler, {Daphne Kaulich} and Pascal Gu{\'e}nel and Qi Guo and Lothar Haeberle and Eric Hahnen and Haiman, {Christopher A.} and Niclas H{\aa}kansson and Emily Hallberg and Ute Hamann and Nathalie Hamel and Susan Hankinson and Hansen, {Thomas V.} and Patricia Harrington and Hart, {Steven N.} and Hartikainen, {Jaana M.} and Healey, {Catherine S.} and Alexander Hein and Sonja Helbig and Alex Henderson and Jane Heyworth and Belynda Hicks and Peter Hillemanns and Shirley Hodgson and Hogervorst, {Frans B.} and Antoinette Hollestelle and Hooning, {Maartje J.} and Bob Hoover and Hopper, {John L.} and Chunling Hu and Guanmengqian Huang and Hulick, {Peter J.} and Keith Humphreys and Hunter, {David J.} and Imyanitov, {Evgeny N.} and Claudine Isaacs and Motoki Iwasaki and Louise Izatt and Anna Jakubowska and Paul James and Ramunas Janavicius and Wolfgang Janni and Jensen, {Uffe Birk} and John, {Esther M.} and Nichola Johnson and Kristine Jones and Michael Jones and Arja Jukkola-Vuorinen and Rudolf Kaaks and Maria Kabisch and Katarzyna Kaczmarek and Daehee Kang and Karin Kast and Renske Keeman and Kerin, {Michael J.} and Kets, {Carolien M.} and Keupers, {Mac Hteld} and Sofia Khan and Elza Khusnutdinova and Kiiski, {Johanna I.} and Kim, {Sung Won} and Knight, {Julia A.} and Irene Konstantopoulou and Kosma, {Veli Matti} and Kristensen, {Vessela N.} and Kruse, {Torben A.} and Ava Kwong and L{\ae}nkholm, {Anne Vibeke} and Yael Laitman and Fiona Lalloo and Diether Lambrechts and Rachel Lloyd and Jennifer Stone",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/ng.3785",

language = "English",

volume = "49",

pages = "1767--1778",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group - Macmillan Publishers",

number = "12",

}

Milne, RL, Kuchenbaecker, KB, Michailidou, K, Beesley, J, Kar, S, Lindström, S, Hui, S, Lemaçon, A, Soucy, P, Dennis, J, Jiang, X, Rostamianfar, A, Finucane, H, Bolla, MK, McGuffog, L, Wang, Q, Aalfs, CM, Abctctb, I, Adams, M, Adlard, J, Agata, S, Ahmed, S, Ahsan, H, Aittom, KÄ, Fares, AE, Allen, J, Ambrosone, CB, Amos, CI, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Arnold, N, Aronson, KJ, Auber, B, Auer, PL, Ausems, MGM, Azzollini, J, François, B, Balma, JN, Barile, M, Barjhoux, L, Barkardottir, RB, Barrdahl, M, Barnes, D, Barrowdale, D, Baynes, C, Beckmann, MW, Benitez, J, Bermisheva, M, Bernstein, L, Bignon, YJ, Blazer, KR, Blok, MJ, Blomqvist, C, Blot, W, Bobolis, K, Boeckx, B, Bogdanova, NV, Bojesen, A, Bojesen, SE, Bonanni, B, Anne-Lise, BD, Bozsik, A, Bradbury, AR, Brand, JS, Brauch, H, Brenner, H, Brigitte, BDP, Brewer, C, Brinton, L, Broberg, P, Angela, BW, Brunet, J, Brüning, T, Burwinkel, B, Buys, SS, Byun, J, Cai, Q, Cald, TÉ, Caligo, MA, Campbell, I, Canzian, F, Caron, O, Carracedo, A, Carter, BD, Esteban, C, Castera, L, Virginie, CM, Chan, SB, Jenny, CC, Chanock, SJ, Chen, X, Cheng, TYD, Chiquette, J, Christiansen, H, Claes, KB, Clarke, CL, Conner, T, Conroy, DM, Cook, J, Cordina-Duverger, E, Cornelissen, S, Coupier, I, Cox, A, Cox, DG, Cross, SS, Cuk, K, Cunningham, JM, Czene, K, Daly, MB, Damiola, F, Darabi, H, Davidson, R, Leeneer, KDL, Devilee, P, Dicks, E, Diez, O, Ding, YC, Ditsch, N, Doheny, KF, Domchek, SM, Dorfling, CM, Dörk, T, Dos-Santos-Silva, I, Dubois, S, Dugué, PA, Dumont, M, Dunning, AM, Durcan, L, Dwek, M, Dworniczak, B, Eccles, D, Eeles, R, Ehrencrona, H, Eilber, U, Ejlertsen, B, Ekici, AB, Eliassen, AH, Engel, C, Eriksson, M, Fachal, L, Faivre, L, Fasching, PA, Faust, U, Figueroa, J, Flesch-Janys, D, Fletcher, O, Flyger, H, Foulkes, WD, Friedman, E, Fritschi, L, Frost, D, Gabrielson, M, Gaddam, P, Gammon, MD, Ganz, PA, Gapstur, SM, Garber, J, Garcia-Barberan, V, Garciá-Saénz, JA, Gaudet, MM, Gauthier-Villars, M, Gehrig, A, Georgoulias, V, Gerdes, AM, Giles, GG, Glendon, G, Godwin, AK, Goldberg, MS, Goldgar, DE, González-Neira, A, Goodfellow, P, Greene, MH, Grenaker, GAI, Grip, M, Gronwald, J, Grundy, A, Gschwantler, DK, Guénel, P, Guo, Q, Haeberle, L, Hahnen, E, Haiman, CA, Håkansson, N, Hallberg, E, Hamann, U, Hamel, N, Hankinson, S, Hansen, TV, Harrington, P, Hart, SN, Hartikainen, JM, Healey, CS, Hein, A, Helbig, S, Henderson, A, Heyworth, J, Hicks, B, Hillemanns, P, Hodgson, S, Hogervorst, FB, Hollestelle, A, Hooning, MJ, Hoover, B, Hopper, JL, Hu, C, Huang, G, Hulick, PJ, Humphreys, K, Hunter, DJ, Imyanitov, EN, Isaacs, C, Iwasaki, M, Izatt, L, Jakubowska, A, James, P, Janavicius, R, Janni, W, Jensen, UB, John, EM, Johnson, N, Jones, K, Jones, M, Jukkola-Vuorinen, A, Kaaks, R, Kabisch, M, Kaczmarek, K, Kang, D, Kast, K, Keeman, R, Kerin, MJ, Kets, CM, Keupers, MH, Khan, S, Khusnutdinova, E, Kiiski, JI, Kim, SW, Knight, JA, Konstantopoulou, I, Kosma, VM, Kristensen, VN, Kruse, TA, Kwong, A, Lænkholm, AV, Laitman, Y, Lalloo, F, Lambrechts, D, Lloyd, R & Stone, J 2017, 'Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer', Nature Genetics, vol. 49, no. 12, pp. 1767-1778. https://doi.org/10.1038/ng.3785

TY - JOUR

T1 - Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

AU - Milne, Roger L.

AU - Kuchenbaecker, Karoline B.

AU - Michailidou, Kyriaki

AU - Beesley, Jonathan

AU - Kar, Siddhartha

AU - Lindström, Sara

AU - Hui, Shirley

AU - Lemaçon, Audrey

AU - Soucy, Penny

AU - Dennis, Joe

AU - Jiang, Xia

AU - Rostamianfar, Asha

AU - Finucane, Hilary

AU - Bolla, Manjeet K.

AU - McGuffog, Lesley

AU - Wang, Qin

AU - Aalfs, Cora M.

AU - Abctctb, Investigators

AU - Adams, Marcia

AU - Adlard, Julian

AU - Agata, Simona

AU - Ahmed, Shahana

AU - Ahsan, Habibul

AU - Aittom, Kristiina Äki

AU - Fares, Al Ejeh

AU - Allen, Jamie

AU - Ambrosone, Christine B.

AU - Amos, Christopher I.

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia N.

AU - Arndt, Volker

AU - Arnold, Norbert

AU - Aronson, Kristan J.

AU - Auber, Bernd

AU - Auer, Paul L.

AU - Ausems, Margreet G.M.

AU - Azzollini, Jacopo

AU - François, Bacot

AU - Balma, Judith Nã

AU - Barile, Monica

AU - Barjhoux, Laure

AU - Barkardottir, Rosa B.

AU - Barrdahl, Myrto

AU - Barnes, Daniel

AU - Barrowdale, Daniel

AU - Baynes, Caroline

AU - Beckmann, Matthias W.

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Bernstein, Leslie

AU - Bignon, Yves Jean

AU - Blazer, Kathleen R.

AU - Blok, Marinus J.

AU - Blomqvist, Carl

AU - Blot, William

AU - Bobolis, Kristie

AU - Boeckx, Bram

AU - Bogdanova, Natalia V.

AU - Bojesen, Anders

AU - Bojesen, Stig E.

AU - Bonanni, Bernardo

AU - Anne-Lise, Børresen Dale

AU - Bozsik, Aniko

AU - Bradbury, Angela R.

AU - Brand, Judith S.

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Brigitte, Bressac De Paillerets

AU - Brewer, Carole

AU - Brinton, Louise

AU - Broberg, Per

AU - Angela, Brooks Wilson

AU - Brunet, Joan

AU - Brüning, Thomas

AU - Burwinkel, Barbara

AU - Buys, Saundra S.

AU - Byun, Jinyoung

AU - Cai, Qiuyin

AU - Cald, Trinidad És

AU - Caligo, Maria A.

AU - Campbell, Ian

AU - Canzian, Federico

AU - Caron, Olivier

AU - Carracedo, Angel

AU - Carter, Brian D.

AU - Esteban, Castelao

AU - Castera, Laurent

AU - Virginie, Caux Moncoutier

AU - Chan, Salina B.

AU - Jenny, Chang Claude

AU - Chanock, Stephen J.

AU - Chen, Xiaoqing

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AU - Lalloo, Fiona

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AU - Lloyd, Rachel

AU - Stone, Jennifer

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

AB - Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=85035773185&partnerID=8YFLogxK

U2 - 10.1038/ng.3785

DO - 10.1038/ng.3785

M3 - Article

C2 - 29058716

AN - SCOPUS:85035773185

SN - 1061-4036

VL - 49

SP - 1767

EP - 1778

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Abstract

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