Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer
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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; Hui, Shirley; Lemaçon, Audrey; Soucy, Penny; Dennis, Joe; Jiang, Xia; Rostamianfar, Asha; Finucane, Hilary; Bolla, Manjeet K; McGuffog, Lesley; Wang, Qin; Aalfs, Cora M; ABCTB Investigators; Adams, Marcia; Adlard, Julian; Agata, Simona; Ahmed, Shahana; Ahsan, Habibul; Aittomäki, Kristiina; Al-Ejeh, Fares; Allen, Jamie; Ambrosone, Christine B; Amos, Christopher I; Andrulis, Irene L; Anton-Culver, Hoda; Antonenkova, Natalia N; Arndt, Volker; Arnold, Norbert; Aronson, Kristan J; Auber, Bernd; Auer, Paul L; Ausems, Margreet G E M; Azzollini, Jacopo; Bacot, François; Balmaña, Judith; Bojesen, Stig E; Gerdes, Anne-Marie; Lænkholm, Anne-Vibeke; Nordestgaard, Børge G; Schmidt, Marjanka K; Antoniou, Antonis C; Simard, Jacques.
I: Nature Genetics, Bind 49, Nr. 12, 2017, s. 1767-1778.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer
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 - ABCTB Investigators
AU - Adams, Marcia
AU - Adlard, Julian
AU - Agata, Simona
AU - Ahmed, Shahana
AU - Ahsan, Habibul
AU - Aittomäki, Kristiina
AU - Al-Ejeh, Fares
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 E M
AU - Azzollini, Jacopo
AU - Bacot, François
AU - Balmaña, Judith
AU - Bojesen, Stig E
AU - Gerdes, Anne-Marie
AU - Lænkholm, Anne-Vibeke
AU - Nordestgaard, Børge G
AU - Schmidt, Marjanka K
AU - Antoniou, Antonis C
AU - Simard, Jacques
PY - 2017
Y1 - 2017
N2 - 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 × 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 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 × 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/genetics
KW - Breast Neoplasms/ethnology
KW - European Continental Ancestry Group/genetics
KW - Female
KW - Genetic Predisposition to Disease/ethnology
KW - Genome-Wide Association Study/methods
KW - Heterozygote
KW - Humans
KW - Mutation
KW - Polymorphism, Single Nucleotide
KW - Receptors, Estrogen/metabolism
KW - Risk Factors
U2 - 10.1038/ng.3785
DO - 10.1038/ng.3785
M3 - Journal article
C2 - 29058716
VL - 49
SP - 1767
EP - 1778
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 12
ER -
ID: 195042726