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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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Nature Communications
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7
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Nature Publishing Group
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  • scopus:84968760294
  • wos:000374894400001
ISSN
2041-1723
DOI
10.1038/ncomms11375
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English
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e4d750b9-0344-4fbf-b263-de87938f5bd0
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2017-02-06 09:37:24
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2017-11-14 09:55:39
@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>},
  articleno    = {11375},
  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. 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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},
  volume       = {7},
  year         = {2016},
}