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; 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 B.M. 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 V.O. Hansen; Steven Hart; Sue Healey; Tuomas Heikkinen; Brian E. Henderson; Josef Herzog; Frans B.L. 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 W.M. 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 A.E.M. Tollenaar; Ian Tomlinson; Thérèse Truong; Helen Tsimiklis; Alex Teulé; Rosario Tumino; Nadine Tung; Clare Turnbull; Giski Ursin; Carolien H.M. 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 D.P. Pharoah; Alvaro A.N. Monteiro; Montserrat García-Closas; Douglas F. Easton; Antonis C. Antoniou

doi:10.1038/ncomms11375

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, Kristiina Aittomäki, Christine Ambrosone, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Banu K. Arun, Brita Arver, Monica Barile, Rosa B. Barkardottir, Daniel BarrowdaleLars 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 B.M. 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 V.O. Hansen, Steven Hart, Sue Healey, Tuomas Heikkinen, Brian E. Henderson, Josef Herzog, Frans B.L. 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 W.M. 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 A.E.M. Tollenaar, Ian Tomlinson, Thérèse Truong, Helen Tsimiklis, Alex Teulé, Rosario Tumino, Nadine Tung, Clare Turnbull, Giski Ursin, Carolien H.M. 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 D.P. Pharoah, Alvaro A.N. Monteiro, Montserrat García-Closas, Douglas F. Easton, Antonis C. Antoniou

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

83 Scopus citations

Abstract

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.

Original language	English
Article number	11375
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11375
State	Published - 27 Apr 2016
Externally published	Yes

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10.1038/ncomms11375

Cite this

Couch, F. J., Kuchenbaecker, K. B., Michailidou, K., Mendoza-Fandino, G. A., Nord, S., Lilyquist, J., Olswold, C., Hallberg, E., Agata, S., Ahsan, H., Aittomäki, K., Ambrosone, C., Andrulis, I. L., Anton-Culver, H., Arndt, V., Arun, B. K., Arver, B., Barile, M., Barkardottir, R. B., ... Antoniou, A. C. (2016). Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer. Nature Communications, 7, Article 11375. https://doi.org/10.1038/ncomms11375

@article{215dca57e05145a492f9bb8e2163644a,

title = "Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer",

abstract = "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.",

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

note = "Funding Information: B.C.A.C. was funded through a European Community Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175; COGS); Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/ A8384, C5047/A15007, C5047/A10692); the National Institutes of Health Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), R01 grants (CA128978, CA176785, CA192393), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative); the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Breast Cancer Res. Foundation, and the Ovarian Cancer Research Fund. CIMBA genotyping was supported by National Institutes of Health grant (CA128978); the Department of Defence (W81XWH-10-1-0341); and the Breast Cancer Res. Foundation. CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A11174 and C1287/A10118.",

year = "2016",

month = apr,

day = "27",

doi = "10.1038/ncomms11375",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

Couch, FJ, Kuchenbaecker, KB, Michailidou, K, Mendoza-Fandino, GA, Nord, S, Lilyquist, J, Olswold, C, Hallberg, E, Agata, S, Ahsan, H, Aittomäki, K, Ambrosone, C, Andrulis, IL, Anton-Culver, H, Arndt, V, Arun, BK, Arver, B, Barile, M, Barkardottir, RB, Barrowdale, D, Beckmann, L, Beckmann, MW, Benitez, J, Blank, SV, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldes, T, Caligo, MA, Canzian, F, Carpenter, J, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Cox, A, Cross, SS, Cunningham, JM, Czene, K, Daly, MB, Damiola, F, Darabi, H, De La Hoya, M, Devilee, P, Diez, O, Ding, YC, Dolcetti, R, Domchek, SM, Dorfling, CM, Dos-Santos-Silva, I, Dumont, M, Dunning, AM, Eccles, DM, Ehrencrona, H, Ekici, AB, Eliassen, H, Ellis, S, Fasching, PA, Figueroa, J, Flesch-Janys, D, Försti, A, Fostira, F, Foulkes, WD, Friebel, T, Friedman, E, Frost, D, Gabrielson, M, Gammon, MD, Ganz, PA, Gapstur, SM, Garber, J, Gaudet, MM, Gayther, SA, Gerdes, AM, Ghoussaini, M, Giles, GG, Glendon, G, Godwin, AK, Goldberg, MS, Goldgar, DE, González-Neira, A, Greene, MH, Gronwald, J, Guénel, P, Gunter, M, Haeberle, L, Haiman, CA, Hamann, U, Hansen, TVO, Hart, S, Healey, S, Heikkinen, T, Henderson, BE, Herzog, J, Hogervorst, FBL, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Humphreys, K, Hunter, DJ, Huzarski, T, Imyanitov, EN, Isaacs, C, Jakubowska, A, James, P, Janavicius, R, Jensen, UB, John, EM, Jones, M, Kabisch, M, Kar, S, Karlan, BY, Khan, S, Khaw, KT, Kibriya, MG, Knight, JA, Ko, YD, Konstantopoulou, I, Kosma, VM, Kristensen, V, Kwong, A, Laitman, Y, Lambrechts, D, Lazaro, C, Lee, E, Le Marchand, L, Lester, J, Lindblom, A, Lindor, N, Lindstrom, S, Liu, J, Long, J, Lubinski, J, Mai, PL, Makalic, E, Malone, KE, Mannermaa, A, Manoukian, S, Margolin, S, Marme, F, Martens, JWM, Mcguffog, L, Meindl, A, Miller, A, Milne, RL, Miron, P, Montagna, M, Mazoyer, S, Mulligan, AM, Muranen, TA, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nordestgaard, BG, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Olson, JE, Osorio, A, Park, SK, Peeters, PH, Peissel, B, Peterlongo, P, Peto, J, Phelan, CM, Pilarski, R, Poppe, B, Pylkäs, K, Radice, P, Rahman, N, Rantala, J, Rappaport, C, Rennert, G, Richardson, A, Robson, M, Romieu, I, Rudolph, A, Rutgers, EJ, Sanchez, MJ, Santella, RM, Sawyer, EJ, Schmidt, DF, Schmidt, MK, Schmutzler, RK, Schumacher, F, Scott, R, Senter, L, Sharma, P, Simard, J, Singer, CF, Sinilnikova, OM, Soucy, P, Southey, M, Steinemann, D, Stenmark-Askmalm, M, Stoppa-Lyonnet, D, Swerdlow, A, Szabo, CI, Tamimi, R, Tapper, W, Teixeira, MR, Teo, SH, Terry, MB, Thomassen, M, Thompson, D, Tihomirova, L, Toland, AE, Tollenaar, RAEM, Tomlinson, I, Truong, T, Tsimiklis, H, Teulé, A, Tumino, R, Tung, N, Turnbull, C, Ursin, G, Van Deurzen, CHM, Van Rensburg, EJ, Varon-Mateeva, R, Wang, Z, Wang-Gohrke, S, Weiderpass, E, Weitzel, JN, Whittemore, A, Wildiers, H, Winqvist, R, Yang, XR, Yannoukakos, D, Yao, S, Zamora, MP, Zheng, W, Hall, P, Kraft, P, Vachon, C, Slager, S, Chenevix-Trench, G, Pharoah, PDP, Monteiro, AAN, García-Closas, M, Easton, DF & Antoniou, AC 2016, 'Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer', Nature Communications, vol. 7, 11375. https://doi.org/10.1038/ncomms11375

TY - JOUR

T1 - Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

AU - Couch, Fergus J.

AU - Kuchenbaecker, Karoline B.

AU - Michailidou, Kyriaki

AU - Mendoza-Fandino, Gustavo A.

AU - Nord, Silje

AU - Lilyquist, Janna

AU - Olswold, Curtis

AU - Hallberg, Emily

AU - Agata, Simona

AU - Ahsan, Habibul

AU - Aittomäki, Kristiina

AU - Ambrosone, Christine

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Arndt, Volker

AU - Arun, Banu K.

AU - Arver, Brita

AU - Barile, Monica

AU - Barkardottir, Rosa B.

AU - Barrowdale, Daniel

AU - Beckmann, Lars

AU - Beckmann, Matthias W.

AU - Benitez, Javier

AU - Blank, Stephanie V.

AU - Blomqvist, Carl

AU - Bogdanova, Natalia V.

AU - Bojesen, Stig E.

AU - Bolla, Manjeet K.

AU - Bonanni, Bernardo

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Burwinkel, Barbara

AU - Buys, Saundra S.

AU - Caldes, Trinidad

AU - Caligo, Maria A.

AU - Canzian, Federico

AU - Carpenter, Jane

AU - Chang-Claude, Jenny

AU - Chanock, Stephen J.

AU - Chung, Wendy K.

AU - Claes, Kathleen B.M.

AU - Cox, Angela

AU - Cross, Simon S.

AU - Cunningham, Julie M.

AU - Czene, Kamila

AU - Daly, Mary B.

AU - Damiola, Francesca

AU - Darabi, Hatef

AU - De La Hoya, Miguel

AU - Devilee, Peter

AU - Diez, Orland

AU - Ding, Yuan C.

AU - Dolcetti, Riccardo

AU - Domchek, Susan M.

AU - Dorfling, Cecilia M.

AU - Dos-Santos-Silva, Isabel

AU - Dumont, Martine

AU - Dunning, Alison M.

AU - Eccles, Diana M.

AU - Ehrencrona, Hans

AU - Ekici, Arif B.

AU - Eliassen, Heather

AU - Ellis, Steve

AU - Fasching, Peter A.

AU - Figueroa, Jonine

AU - Flesch-Janys, Dieter

AU - Försti, Asta

AU - Fostira, Florentia

AU - Foulkes, William D.

AU - Friebel, Tara

AU - Friedman, Eitan

AU - Frost, Debra

AU - Gabrielson, Marike

AU - Gammon, Marilie D.

AU - Ganz, Patricia A.

AU - Gapstur, Susan M.

AU - Garber, Judy

AU - Gaudet, Mia M.

AU - Gayther, Simon A.

AU - Gerdes, Anne Marie

AU - Ghoussaini, Maya

AU - Giles, Graham G.

AU - Glendon, Gord

AU - Godwin, Andrew K.

AU - Goldberg, Mark S.

AU - Goldgar, David E.

AU - González-Neira, Anna

AU - Greene, Mark H.

AU - Gronwald, Jacek

AU - Guénel, Pascal

AU - Gunter, Marc

AU - Haeberle, Lothar

AU - Haiman, Christopher A.

AU - Hamann, Ute

AU - Hansen, Thomas V.O.

AU - Hart, Steven

AU - Healey, Sue

AU - Heikkinen, Tuomas

AU - Henderson, Brian E.

AU - Herzog, Josef

AU - Hogervorst, Frans B.L.

AU - Hollestelle, Antoinette

AU - Hooning, Maartje J.

AU - Hoover, Robert N.

AU - Hopper, John L.

AU - Humphreys, Keith

AU - Hunter, David J.

AU - Huzarski, Tomasz

AU - Imyanitov, Evgeny N.

AU - Isaacs, Claudine

AU - Jakubowska, Anna

AU - James, Paul

AU - Janavicius, Ramunas

AU - Jensen, Uffe Birk

AU - John, Esther M.

AU - Jones, Michael

AU - Kabisch, Maria

AU - Kar, Siddhartha

AU - Karlan, Beth Y.

AU - Khan, Sofia

AU - Khaw, Kay Tee

AU - Kibriya, Muhammad G.

AU - Knight, Julia A.

AU - Ko, Yon Dschun

AU - Konstantopoulou, Irene

AU - Kosma, Veli Matti

AU - Kristensen, Vessela

AU - Kwong, Ava

AU - Laitman, Yael

AU - Lambrechts, Diether

AU - Lazaro, Conxi

AU - Lee, Eunjung

AU - Le Marchand, Loic

AU - Lester, Jenny

AU - Lindblom, Annika

AU - Lindor, Noralane

AU - Lindstrom, Sara

AU - Liu, Jianjun

AU - Long, Jirong

AU - Lubinski, Jan

AU - Mai, Phuong L.

AU - Makalic, Enes

AU - Malone, Kathleen E.

AU - Mannermaa, Arto

AU - Manoukian, Siranoush

AU - Margolin, Sara

AU - Marme, Frederik

AU - Martens, John W.M.

AU - Mcguffog, Lesley

AU - Meindl, Alfons

AU - Miller, Austin

AU - Milne, Roger L.

AU - Miron, Penelope

AU - Montagna, Marco

AU - Mazoyer, Sylvie

AU - Mulligan, Anna M.

AU - Muranen, Taru A.

AU - Nathanson, Katherine L.

AU - Neuhausen, Susan L.

AU - Nevanlinna, Heli

AU - Nordestgaard, Børge G.

AU - Nussbaum, Robert L.

AU - Offit, Kenneth

AU - Olah, Edith

AU - Olopade, Olufunmilayo I.

AU - Olson, Janet E.

AU - Osorio, Ana

AU - Park, Sue K.

AU - Peeters, Petra H.

AU - Peissel, Bernard

AU - Peterlongo, Paolo

AU - Peto, Julian

AU - Phelan, Catherine M.

AU - Pilarski, Robert

AU - Poppe, Bruce

AU - Pylkäs, Katri

AU - Radice, Paolo

AU - Rahman, Nazneen

AU - Rantala, Johanna

AU - Rappaport, Christine

AU - Rennert, Gad

AU - Richardson, Andrea

AU - Robson, Mark

AU - Romieu, Isabelle

AU - Rudolph, Anja

AU - Rutgers, Emiel J.

AU - Sanchez, Maria Jose

AU - Santella, Regina M.

AU - Sawyer, Elinor J.

AU - Schmidt, Daniel F.

AU - Schmidt, Marjanka K.

AU - Schmutzler, Rita K.

AU - Schumacher, Fredrick

AU - Scott, Rodney

AU - Senter, Leigha

AU - Sharma, Priyanka

AU - Simard, Jacques

AU - Singer, Christian F.

AU - Sinilnikova, Olga M.

AU - Soucy, Penny

AU - Southey, Melissa

AU - Steinemann, Doris

AU - Stenmark-Askmalm, Marie

AU - Stoppa-Lyonnet, Dominique

AU - Swerdlow, Anthony

AU - Szabo, Csilla I.

AU - Tamimi, Rulla

AU - Tapper, William

AU - Teixeira, Manuel R.

AU - Teo, Soo Hwang

AU - Terry, Mary B.

AU - Thomassen, Mads

AU - Thompson, Deborah

AU - Tihomirova, Laima

AU - Toland, Amanda E.

AU - Tollenaar, Robert A.E.M.

AU - Tomlinson, Ian

AU - Truong, Thérèse

AU - Tsimiklis, Helen

AU - Teulé, Alex

AU - Tumino, Rosario

AU - Tung, Nadine

AU - Turnbull, Clare

AU - Ursin, Giski

AU - Van Deurzen, Carolien H.M.

AU - Van Rensburg, Elizabeth J.

AU - Varon-Mateeva, Raymonda

AU - Wang, Zhaoming

AU - Wang-Gohrke, Shan

AU - Weiderpass, Elisabete

AU - Weitzel, Jeffrey N.

AU - Whittemore, Alice

AU - Wildiers, Hans

AU - Winqvist, Robert

AU - Yang, Xiaohong R.

AU - Yannoukakos, Drakoulis

AU - Yao, Song

AU - Zamora, M. Pilar

AU - Zheng, Wei

AU - Hall, Per

AU - Kraft, Peter

AU - Vachon, Celine

AU - Slager, Susan

AU - Chenevix-Trench, Georgia

AU - Pharoah, Paul D.P.

AU - Monteiro, Alvaro A.N.

AU - García-Closas, Montserrat

AU - Easton, Douglas F.

AU - Antoniou, Antonis C.

N1 - Funding Information: B.C.A.C. was funded through a European Community Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175; COGS); Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/ A8384, C5047/A15007, C5047/A10692); the National Institutes of Health Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), R01 grants (CA128978, CA176785, CA192393), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative); the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Breast Cancer Res. Foundation, and the Ovarian Cancer Research Fund. CIMBA genotyping was supported by National Institutes of Health grant (CA128978); the Department of Defence (W81XWH-10-1-0341); and the Breast Cancer Res. Foundation. CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A11174 and C1287/A10118.

PY - 2016/4/27

Y1 - 2016/4/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84968760294&partnerID=8YFLogxK

U2 - 10.1038/ncomms11375

DO - 10.1038/ncomms11375

M3 - Article

C2 - 27117709

AN - SCOPUS:84968760294

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11375

ER -

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

Abstract

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