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

Couch, Fergus J ; Kuchenbaecker, Karoline B. ; Michailidou, Kyriaki ; Mendoza-Fandino, Gustavo A. ; Nord, Silje ; Lilyquist, Janna ; Olswold, Curtis ; Hallberg, Emily ; Agata, Simona and Ahsan, Habibul , et al. (2016) In Nature Communications 7.
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... (More)

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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publishing date
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Contribution to journal
publication status
published
subject
in
Nature Communications
volume
7
article number
11375
publisher
Nature Publishing Group
external identifiers
  • scopus:84968760294
  • pmid:27117709
  • wos:000374894400001
ISSN
2041-1723
DOI
10.1038/ncomms11375
language
English
LU publication?
yes
id
e4d750b9-0344-4fbf-b263-de87938f5bd0
date added to LUP
2017-02-06 09:37:24
date last changed
2024-04-14 03:36:14
@article{e4d750b9-0344-4fbf-b263-de87938f5bd0,
  abstract     = {{<p>Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P&lt;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&lt;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.</p>}},
  author       = {{Couch, Fergus J and Kuchenbaecker, Karoline B. and Michailidou, Kyriaki and Mendoza-Fandino, Gustavo A. and Nord, Silje and Lilyquist, Janna and Olswold, Curtis and Hallberg, Emily and Agata, Simona and Ahsan, Habibul and Aittomäki, Kristiina and Ambrosone, Christine and Andrulis, Irene L and Anton-Culver, Hoda and Arndt, Volker and Arun, Banu K. and Arver, Brita and Barile, Monica and Barkardottir, Rosa B. and Barrowdale, Daniel and Beckmann, Lars and Beckmann, Matthias W and Benitez, Javier and Blank, Stephanie V. and Blomqvist, Carl and Bogdanova, Natalia V and Bojesen, Stig E and Bolla, Manjeet K and Bonanni, Bernardo and Brauch, Hiltrud and Brenner, Hermann and Burwinkel, Barbara and Buys, Saundra and Caldes, Trinidad and Caligo, Maria A. and Canzian, Federico and Carpenter, Jane and Chang-Claude, Jenny and Chanock, Stephen J and Chung, Wendy K. and Claes, Kathleen B M and Cox, Angela and Cross, Simon S and Cunningham, Julie M. and Czene, Kamila and Daly, Mary B. and Damiola, Francesca and Darabi, Hatef and de la Hoya, Miguel and Devilee, Peter and Diez, Orland and Ding, Yuan C. and Dolcetti, Riccardo and Domchek, Susan M and Dorfling, Cecilia M. and Dos Santos Silva, Isabel and Dumont, Martine and Dunning, Alison M. and Eccles, Diana M. and Ehrencrona, Hans and Ekici, Arif B and Eliassen, A Heather and Ellis, Steve and Fasching, Peter A and Figueroa, Jonine and Flesch-Janys, Dieter and Försti, Asta and Fostira, Florentia and Foulkes, William D and Friebel, Tara and Friedman, Eitan and Frost, Debra and Gabrielson, Marike and Gammon, Marilie D. and Ganz, Patricia A. and Gapstur, Susan M and Garber, Judy and Gaudet, Mia and Gayther, Simon A. and Gerdes, Anne-Marie and Ghoussaini, Maya and Giles, Graham G and Glendon, Gord and Godwin, Andrew K and Goldberg, Mark S and Goldgar, David E. and González-Neira, Anna and Greene, Mark H and Gronwald, Jacek and Guénel, Pascal and Gunter, Marc and Haeberle, Lothar and Haiman, Christopher A. and Hamann, Ute and Hansen, Thomas V. O. and Hart, Steven and Healey, Sue and Heikkinen, Tuomas and Henderson, Brian E. and Herzog, Josef and Hogervorst, Frans B. L. and Hollestelle, Antoinette and Hooning, Maartje J. and Hoover, Robert N. and Hopper, John L and Humphreys, Keith and Hunter, David J and Huzarski, Tomasz and Imyanitov, Evgeny N and Isaacs, Claudine and Jakubowska, Anna and James, Paul and Janavicius, Ramunas and Jensen, Uffe Birk and John, Esther M. and Jones, Michael and Kabisch, Maria and Kar, Siddhartha and Karlan, Beth Y. and Khan, Sofia and Khaw, Kay Tee and Kibriya, Muhammad G and Knight, Julia A and Ko, Yon-Dschun and Konstantopoulou, Irene and Kosma, Veli-Matti and Kristensen, Vessela and Kwong, Ava and Laitman, Yael and Lambrechts, Diether and Lazaro, Conxi and Lee, Eunjung and Le Marchand, Loic and Lester, Jenny and Lindblom, Annika and Lindor, Noralane and Lindstrom, Sara and Liu, Jianjun and Long, Jirong and Lubinski, Jan and Mai, Phuong L and Makalic, Enes and Malone, Kathleen E and Mannermaa, Arto and Manoukian, Siranoush and Margolin, Sara and Marme, Frederik and Martens, John W M and McGuffog, Lesley and Meindl, Alfons and Miller, Austin and Milne, Roger L. and Miron, Penelope and Montagna, Marco and Mazoyer, Sylvie and Mulligan, Anna Marie and Muranen, Taru A. and Nathanson, Katherine L and Neuhausen, Susan L. and Nevanlinna, Heli and Nordestgaard, Børge G and Nussbaum, Robert L and Offit, Kenneth and Olah, Edith and Olopade, Olufunmilayo I. and Olson, Janet E and Osorio, Ana and Park, Sue K. and Peeters, Petra H. and Peissel, Bernard and Peterlongo, Paolo and Peto, Julian and Phelan, Catherine M. and Pilarski, Robert and Poppe, Bruce and Pylkäs, Katri and Radice, Paolo and Rahman, Nazneen and Rantala, Johanna and Rappaport, Christine and Rennert, Gad and Richardson, Andrea L. and Robson, Mark and Romieu, Isabelle and Rudolph, Anja 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 Schumacher, Fredrick and Scott, Rodney and Senter, Leigha and Sharma, Priyanka and Simard, Jacques and Singer, Christian F. and Sinilnikova, Olga M and Soucy, Penny and Southey, Melissa and Steinemann, Doris and Stenmark-Askmalm, Marie and Stoppa-Lyonnet, Dominique and Swerdlow, Anthony and Szabo, Csilla I and Tamimi, Rulla and Tapper, William and Teixeira, Manuel R and Teo, Soo-Hwang and Terry, Mary B. and Thomassen, Mads and Thompson, Deborah and Tihomirova, Laima and Toland, Amanda E and Tollenaar, Robert A E M and Tomlinson, Ian and Truong, Thérèse and Tsimiklis, Helen and Teulé, Alex and Tumino, Rosario and Tung, Nadine and Turnbull, Clare and Ursin, Giski and van Deurzen, Carolien H. M. and van Rensburg, Elizabeth J. and Varon-Mateeva, Raymonda and Wang, Zhaoming and Wang-Gohrke, Shan and Weiderpass, Elisabete and Weitzel, Jeffrey N. and Whittemore, Alice S. and Wildiers, Hans and Winqvist, Robert and Yang, Xiaohong R and Yannoukakos, Drakoulis and Yao, Song and Zamora, M Pilar and Zheng, Wei and Hall, Per and Kraft, Peter and Vachon, Celine and Slager, Susan and Chenevix-Trench, Georgia and Pharoah, Paul P. D. and Monteiro, Alvaro N and García-Closas, Montserrat and Easton, Douglas F and Antoniou, Antonis C}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  month        = {{04}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer}},
  url          = {{http://dx.doi.org/10.1038/ncomms11375}},
  doi          = {{10.1038/ncomms11375}},
  volume       = {{7}},
  year         = {{2016}},
}