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

Milne, Roger L; Kuchenbaecker, Karoline B.; Michailidou, Kyriaki; Beesley, Jonathan; Kar, Siddhartha; Lindström, Sara ; Broberg, Per LU ; Olsson, Håkan LU and Ehrencrona, Hans LU (2017) In Nature Genetics 49(12). p.1767-1778
Abstract
Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. 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 × 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%... (More)
Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. 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 × 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. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
49
issue
12
pages
12 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85035773185
ISSN
1546-1718
DOI
10.1038/ng.3785
language
English
LU publication?
yes
id
80e5ba7e-9962-4e62-806d-50d4dd989868
date added to LUP
2017-12-14 14:58:24
date last changed
2018-05-20 04:39:24
@article{80e5ba7e-9962-4e62-806d-50d4dd989868,
  abstract     = {Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. 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 &lt; 5 × 10-8 with ten variants at nine new loci. At P &lt; 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.},
  author       = {Milne, Roger L and Kuchenbaecker, Karoline B. and Michailidou, Kyriaki and Beesley, Jonathan and Kar, Siddhartha and Lindström, Sara  and Broberg, Per and Olsson, Håkan and Ehrencrona, Hans},
  issn         = {1546-1718},
  language     = {eng},
  number       = {12},
  pages        = {1767--1778},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer},
  url          = {http://dx.doi.org/10.1038/ng.3785},
  volume       = {49},
  year         = {2017},
}