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 B 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 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 D Ellis; Peter A Fasching; Jonine Figueroa; Dieter Flesch-Janys; Asta Försti; Florentia Fostira; William D Foulkes; Tara M Friebel; Eitan Friedman; Debra Frost; Marike Gabrielson; Marilie D Gammon; Patricia A Ganz; Susan M Gapstur; Judy Garber; Mia Gaudet; Simon A Gayther; Anne-Marie Gerdes; Maya Ghoussaini; Graham Giles; Gord Glendon; Andrew K Godwin; Mark S Goldberg; David E Goldgar; Anna González-Neira; Mark H Greene; Jacek Gronwald; Pascal Guénel; Marc J Gunter; Lothar Haeberle; Christopher A Haiman; Ute Hamann; Thomas v O Hansen; Steven N 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 Marie 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 L Richardson; Mark Robson; Isabelle Romieu; Anja Rudolph; Emiel J Rutgers; Maria-José Sánchez; Regina M Santella; Elinor J Sawyer; Daniel F Schmidt; Marjanka K Schmidt; Rita K Schmutzler; Fredrick Schumacher; Rodney J 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; Therese 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 S 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 P D Pharoah; Alvaro N A 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 B 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 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 D Ellis, Peter A Fasching, Jonine Figueroa, Dieter Flesch-Janys, Asta Försti, Florentia Fostira, William D Foulkes, Tara M Friebel, Eitan Friedman, Debra Frost, Marike Gabrielson, Marilie D Gammon, Patricia A Ganz, Susan M Gapstur, Judy Garber, Mia Gaudet, Simon A Gayther, Anne-Marie Gerdes, Maya Ghoussaini, Graham Giles, Gord Glendon, Andrew K Godwin, Mark S Goldberg, David E Goldgar, Anna González-Neira, Mark H Greene, Jacek Gronwald, Pascal Guénel, Marc J Gunter, Lothar Haeberle, Christopher A Haiman, Ute Hamann, Thomas v O Hansen, Steven N 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 Marie 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 L Richardson, Mark Robson, Isabelle Romieu, Anja Rudolph, Emiel J Rutgers, Maria-José Sánchez, Regina M Santella, Elinor J Sawyer, Daniel F Schmidt, Marjanka K Schmidt, Rita K Schmutzler, Fredrick Schumacher, Rodney J 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, Therese 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 S 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 P D Pharoah, Alvaro N A Monteiro, Montserrat García-Closas, Douglas F Easton, Antonis C Antoniou

Department of Clinical Medicine

55 Citations (Scopus)

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
Pages (from-to)	1-13
Number of pages	13
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms11375
Publication status	Published - 27 Apr 2016

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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. B., 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, 1-13. [11375]. https://doi.org/10.1038/ncomms11375

Couch, FJ, Kuchenbaecker, KB, Michailidou, K, Mendoza-Fandino, GA, Nord, S, Lilyquist, J, Olswold, C, Hallberg, E, Agata, S, Ahsan, H, Aittomäki, K, Ambrosone, CB, 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, S, 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, SD, Fasching, PA, Figueroa, J, Flesch-Janys, D, Försti, A, Fostira, F, Foulkes, WD, Friebel, TM, Friedman, E, Frost, D, Gabrielson, M, Gammon, MD, Ganz, PA, Gapstur, SM, Garber, J, Gaudet, M, Gayther, SA, Gerdes, A-M, Ghoussaini, M, Giles, G, Glendon, G, Godwin, AK, Goldberg, MS, Goldgar, DE, González-Neira, A, Greene, MH, Gronwald, J, Guénel, P, Gunter, MJ, Haeberle, L, Haiman, CA, Hamann, U, Hansen, TVO, Hart, SN, 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, K-T, Kibriya, MG, Knight, JA, Ko, Y-D, Konstantopoulou, I, Kosma, V-M, 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, AL, Robson, M, Romieu, I, Rudolph, A, Rutgers, EJ, Sánchez, M-J, Santella, RM, Sawyer, EJ, Schmidt, DF, Schmidt, MK, Schmutzler, RK, Schumacher, F, Scott, RJ, 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, S-H, 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, AS, 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, PPD, Monteiro, ANA, 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, pp. 1-13. https://doi.org/10.1038/ncomms11375

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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 × 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.",

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doi = "10.1038/ncomms11375",

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journal = "Nature Communications",

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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 B

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

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 D

AU - Fasching, Peter A

AU - Figueroa, Jonine

AU - Flesch-Janys, Dieter

AU - Försti, Asta

AU - Fostira, Florentia

AU - Foulkes, William D

AU - Friebel, Tara M

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

AU - Gayther, Simon A

AU - Gerdes, Anne-Marie

AU - Ghoussaini, Maya

AU - Giles, Graham

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 J

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AU - Antoniou, Antonis C

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.

KW - Journal Article

U2 - 10.1038/ncomms11375

DO - 10.1038/ncomms11375

M3 - Journal article

C2 - 27117709

SN - 2041-1723

VL - 7

SP - 1

EP - 13

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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