Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- Author(s): Couch, FJ
- Kuchenbaecker, KB
- Michailidou, K
- Mendoza-Fandino, GA
- Nord, S
- Lilyquist, J
- Olswold, C
- Hallberg, E
- Agata, S
- Ahsan, H
- Aittomäki, K
- Ambrosone, C
- Andrulis, IL
- Anton-Culver, H
- Arndt, V
- Arun, BK
- Arver, B
- Barile, M
- Barkardottir, RB
- Barrowdale, D
- Beckmann, L
- Beckmann, MW
- Benitez, J
- Blank, SV
- Blomqvist, C
- Bogdanova, NV
- Bojesen, SE
- Bolla, MK
- Bonanni, B
- Brauch, H
- Brenner, H
- Burwinkel, B
- Buys, SS
- Caldes, T
- Caligo, MA
- Canzian, F
- Carpenter, J
- Chang-Claude, J
- Chanock, SJ
- Chung, WK
- Claes, KBM
- Cox, A
- Cross, SS
- Cunningham, JM
- Czene, K
- Daly, MB
- Damiola, F
- Darabi, H
- De La Hoya, M
- Devilee, P
- Diez, O
- Ding, YC
- Dolcetti, R
- Domchek, SM
- Dorfling, CM
- Dos-Santos-Silva, I
- Dumont, M
- Dunning, AM
- Eccles, DM
- Ehrencrona, H
- Ekici, AB
- Eliassen, H
- Ellis, S
- Fasching, PA
- Figueroa, J
- Flesch-Janys, D
- Försti, A
- Fostira, F
- Foulkes, WD
- Friebel, T
- Friedman, E
- Frost, D
- Gabrielson, M
- Gammon, MD
- Ganz, PA
- Gapstur, SM
- Garber, J
- Gaudet, MM
- Gayther, SA
- Gerdes, AM
- Ghoussaini, M
- Giles, GG
- Glendon, G
- Godwin, AK
- Goldberg, MS
- Goldgar, DE
- González-Neira, A
- Greene, MH
- Gronwald, J
- Guénel, P
- Gunter, M
- Haeberle, L
- Haiman, CA
- et al.
Published Web Location
https://doi.org/10.1038/ncomms11375Abstract
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.
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