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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

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  • Kyriaki Michailidou
  • Gustavo A Mendoza-Fandino
  • Silje Nord
  • Janna Lilyquist
  • Curtis Olswold
  • Emily Hallberg
  • Simona Agata
  • Habibul Ahsan
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  • Christine Ambrosone
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  • Hoda Anton-Culver
  • Volker Arndt
  • Banu K Arun
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  • Monica Barile
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Vis graf over relationer

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

OriginalsprogEngelsk
TidsskriftNature Communications
Vol/bind7
Sider (fra-til)11375
ISSN2041-1723
DOI
StatusUdgivet - 27 apr. 2016

ID: 49235475