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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
Mayo Clin, MN 55905 USA; Mayo Clin, MN 55905 USA.
University of Cambridge, England.
University of Cambridge, England.
University of S Florida, FL 33612 USA.
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2016 (engelsk)Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, nr 11375, s. 1-13Artikkel i tidsskrift (Fagfellevurdert) Published
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Abstract [en]

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 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 similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

sted, utgiver, år, opplag, sider
NATURE PUBLISHING GROUP , 2016. Vol. 7, nr 11375, s. 1-13
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URN: urn:nbn:se:liu:diva-128757DOI: 10.1038/ncomms11375ISI: 000374894400001PubMedID: 27117709OAI: oai:DiVA.org:liu-128757DiVA, id: diva2:931925
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Funding Agencies|European Community Seventh Framework Programme [223175, HEALTH-F2-2009-223175]; Cancer Research UK [C1287/A10118, C1287/A10710, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C12292/A11174]; National Institutes of Health [CA116201, CA128978, CA176785, CA192393]; National Institutes of Health, Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; National Institutes of Health, GAME-ON initiative; Canadian Institutes of Health Research (CIHR); Breast Cancer Res. Foundation; Ovarian Cancer Research Fund; Department of Defence [W81XWH-10-1-0341]; Florida Breast Cancer Foundation

Tilgjengelig fra: 2016-05-31 Laget: 2016-05-30 Sist oppdatert: 2017-11-30

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