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

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Title:	Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer
Author(s):	Milne, R.L.; Kuchenbaecker, K.B.; Michailidou, K.; Beesley, J.; Kar, S.; Lindstrom, S.; Hui, S.; Lemacon, A.; Soucy, P.; Dennis, J.; Jiang, X; Rostamianfar, A.; Finucane, H.; Bolla, M.K.; McGuffog, L.; Wang, Q.; Aalfs, C.M.; Adams, M.; Adlard, J.; Agata, S.; Ahmed, S.; Ahsan, H.; Aittomaki, K.; Al-Ejeh, F.; Allen, J.; Ambrosone, C.B.; Amos, C.I.; Andrulis, I.L.; Anton-Culver, H.; Antonenkova, N.N.; Arndt, V.; Arnold, N.; Aronson, K.J.; Auber, B.; Auer, P.L.; Ausems, M.; Azzollini, J.; Bacot, F.; Balmana, J.; Barile, M.; Barjhoux, L.; Barkardottir, R.B.; Barrdahl, M.; Barnes, D.; Barrowdale, D.; Baynes, C.; Beckmann, M.W.; Benitez, J.; Bermisheva, M.; Bernstein, L.; Bignon, Y.J.; Blazer, K.R.; Blok, M.J.; Blomqvist, C.; Blot, W.; Bobolis, K.; Boeckx, B.; Bogdanova, N.V.; Bojesen, A.; Bojesen, S.E.; Bonanni, B.; Borresen-Dale, A.L.; Bozsik, A.; Bradbury, A.R.; Brand, J.S.; Brauch, H.; Brenner, H.; Bressac-de Paillerets, B.; Brewer, C.; Brinton, L.; Broberg, P.; Brooks-Wilson, A.; Brunet, J.; Bruning, T.; Burwinkel, B.; Buys, S.S.; Byun, J.; Cai, Q.; Caldes, T.; Caligo, M.A.; Campbell, I.; Canzian, F.; Caron, O.; Carracedo, A.; Carter, B.D.; Castelao, J.E.; Castera, L.; Caux-Moncoutier, V.; Chan, S.B.; Chang-Claude, J.; Chanock, S.J.; Chen, X; Cheng, T.D.; Chiquette, J.; Christiansen, H.; Claes, K.B.M.; Clarke, C.L.; Conner, T.; Conroy, D.M.; Cook, J.; Kets, C.M. ; Simard, J.
Publication year:	2017
Source:	Nature Genetics, vol. 49, iss. 12, (2017), pp. 1767-1778
ISSN:	1061-4036
DOI:	https://doi.org/10.1038/ng.3785
Publication type:	Article / Letter to editor
Please use this identifier to cite or link to this item : https://hdl.handle.net/2066/182762
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Subject:	Radboudumc 17: Women's cancers RIHS: Radboud Institute for Health Sciences Tijdelijke code tbv inlezen publicaties Radboudumc - Alleen voor gebruik door Radboudumc
Organization:	Human Genetics
Journal title:	Nature Genetics
Volume:	vol. 49
Issue:	iss. 12
Page start:	p. 1767
Page end:	p. 1778
Abstract:	Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. 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 x 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.