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

the Breast Cancer Association Consortium (BCAC); the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA); ABCTB Investigators; Roger L. Milne; Judith S. Brand; Kenneth Muir; Antonis C. Antoniou

doi:10.1038/ng.3785

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

the Breast Cancer Association Consortium (BCAC), the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), ABCTB Investigators, Roger L. Milne^*, Judith S. Brand, Kenneth Muir, Antonis C. Antoniou

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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% 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.

Original language	English
Pages (from-to)	1767-1778
Number of pages	12
Journal	Nature Genetics
Volume	49
Issue number	12
Early online date	23 Oct 2017
DOIs	https://doi.org/10.1038/ng.3785
Publication status	Published - 1 Dec 2017

Keywords

BRCA1 Protein
Breast Neoplasms
European Continental Ancestry Group
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Heterozygote
Humans
Mutation
Polymorphism, Single Nucleotide
Receptors, Estrogen
Risk Factors
Journal Article

UN SDGs

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

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@article{93c8f17d3c9449ada0d0dbd5bf82a241,

title = "Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer",

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% 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.",

keywords = "BRCA1 Protein, Breast Neoplasms, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Heterozygote, Humans, Mutation, Polymorphism, Single Nucleotide, Receptors, Estrogen, Risk Factors, Journal Article",

author = "{the Breast Cancer Association Consortium (BCAC)} and {the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)} and {ABCTB Investigators} and Milne, {Roger L.} and Kuchenbaecker, {Karoline B.} and Kyriaki Michailidou and Jonathan Beesley and Siddhartha Kar and Sara Lindstr{\"o}m and Shirley Hui and Audrey Lema{\c c}on and Penny Soucy and Joe Dennis and Xia Jiang and Asha Rostamianfar and Hilary Finucane and Bolla, {Manjeet K.} and Lesley McGuffog and Qin Wang and Aalfs, {Cora M.} and Marcia Adams and Julian Adlard and Simona Agata and Shahana Ahmed and Habibul Ahsan and Aittom, {Kristiina {\"A}ki} and Fares, {Al Ejeh} and Jamie Allen and Ambrosone, {Christine B.} and Amos, {Christopher I.} and Andrulis, {Irene L.} and Hoda Anton-Culver and Antonenkova, {Natalia N.} and Volker Arndt and Norbert Arnold and Aronson, {Kristan J.} and Bernd Auber and Auer, {Paul L.} and Ausems, {Margreet G.M.} and Jacopo Azzollini and Bacot Fran{\c c}ois and Balma, {Judith N{\~a}} and Monica Barile and Laure Barjhoux and Barkardottir, {Rosa B.} and Myrto Barrdahl and Daniel Barnes and Daniel Barrowdale and Brand, {Judith S.} and Kenneth Muir and Side, {Lucy E.} and Antoniou, {Antonis C.}",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/ng.3785",

language = "English",

volume = "49",

pages = "1767--1778",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Springer Nature",

number = "12",

}

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. / the Breast Cancer Association Consortium (BCAC); the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA); ABCTB Investigators et al.
In: Nature Genetics, Vol. 49, No. 12, 01.12.2017, p. 1767-1778.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

AU - the Breast Cancer Association Consortium (BCAC)

AU - the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

AU - ABCTB Investigators

AU - Milne, Roger L.

AU - Kuchenbaecker, Karoline B.

AU - Michailidou, Kyriaki

AU - Beesley, Jonathan

AU - Kar, Siddhartha

AU - Lindström, Sara

AU - Hui, Shirley

AU - Lemaçon, Audrey

AU - Soucy, Penny

AU - Dennis, Joe

AU - Jiang, Xia

AU - Rostamianfar, Asha

AU - Finucane, Hilary

AU - Bolla, Manjeet K.

AU - McGuffog, Lesley

AU - Wang, Qin

AU - Aalfs, Cora M.

AU - Adams, Marcia

AU - Adlard, Julian

AU - Agata, Simona

AU - Ahmed, Shahana

AU - Ahsan, Habibul

AU - Aittom, Kristiina Äki

AU - Fares, Al Ejeh

AU - Allen, Jamie

AU - Ambrosone, Christine B.

AU - Amos, Christopher I.

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia N.

AU - Arndt, Volker

AU - Arnold, Norbert

AU - Aronson, Kristan J.

AU - Auber, Bernd

AU - Auer, Paul L.

AU - Ausems, Margreet G.M.

AU - Azzollini, Jacopo

AU - François, Bacot

AU - Balma, Judith Nã

AU - Barile, Monica

AU - Barjhoux, Laure

AU - Barkardottir, Rosa B.

AU - Barrdahl, Myrto

AU - Barnes, Daniel

AU - Barrowdale, Daniel

AU - Brand, Judith S.

AU - Muir, Kenneth

AU - Side, Lucy E.

AU - Antoniou, Antonis C.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

KW - BRCA1 Protein

KW - Breast Neoplasms

KW - European Continental Ancestry Group

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Heterozygote

KW - Humans

KW - Mutation

KW - Polymorphism, Single Nucleotide

KW - Receptors, Estrogen

KW - Risk Factors

KW - Journal Article

UR - http://www.scopus.com/inward/record.url?scp=85035773185&partnerID=8YFLogxK

U2 - 10.1038/ng.3785

DO - 10.1038/ng.3785

M3 - Article (Academic Journal)

C2 - 29058716

SN - 1061-4036

VL - 49

SP - 1767

EP - 1778

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

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

Abstract

Keywords

UN SDGs

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