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