M Ghoussaini, O Fletcher, K Michailidou, C Turnbull, MK Schmidt, E Dicks, J Dennis, Q Wang, MK Humphreys, C Luccarini, C Baynes, D Conroy, M Maranian, S Ahmed, K Driver, N Johnson, N Orr, I dos Santos Silva, Q Waisfisz, H Meijers-Heijboer, AG Uitterlinden, F Rivadeneira, Netherlands Collaborative Group on Hereditary Breast and Ovarian Cancer (HEBON), P Hall, K Czene, A Irwanto, J Liu, H Nevanlinna, K Aittomäki, C Blomqvist, A Meindl, RK Schmutzler, B Müller-Myhsok, P Lichtner, J Chang-Claude, R Hein, S Nickels, D Flesch-Janys, H Tsimiklis, E Makalic, D Schmidt, M Bui, JL Hopper, C Apicella, DJ Park, M Southey, DJ Hunter, SJ Chanock, A Broeks, S Verhoef, FBL Hogervorst, PA Fasching, MP Lux, MW Beckmann, AB Ekici, E Sawyer, I Tomlinson, M Kerin, F Marme, A Schneeweiss, C Sohn, B Burwinkel, P Guénel, T Truong, E Cordina-Duverger, F Menegaux, SE Bojesen, BG Nordestgaard, SF Nielsen, H Flyger, RL Milne, MR Alonso, A González-Neira, J Benítez, H Anton-Culver, A Ziogas, L Bernstein, CC Dur, H Brenner, H Müller, V Arndt, C Stegmaier, Familial Breast Cancer Study (FBCS), C Justenhoven, H Brauch, T Brüning, Gene Environment Interaction of Breast Cancer in Germany (GENICA) Network, S Wang-Gohrke, U Eilber, T Dörk, P Schürmann, M Bremer, P Hillemanns, NV Bogdanova, NN Antonenkova, YI Rogov, JH Karstens, M Bermisheva, D Prokofieva, E Khusnutdinova, A Lindblom, S Margolin, A Mannermaa, V Kataja, V-M Kosma, JM Hartikainen, D Lambrechts, BT Yesilyurt, G Floris, K Leunen, S Manoukian, B Bonanni, S Fortuzzi, P Peterlongo, FJ Couch, X Wang, K Stevens, A Lee, GG Giles, L Baglietto, G Severi, C McLean, GG Alnaes, V Kristensen, A-L Børrensen-Dale, EM John, A Miron, R Winqvist, K Pylkäs, A Jukkola-Vuorinen, S Kauppila, IL Andrulis, G Glendon, AM Mulligan, P Devilee, CJ van Asperen, RAEM Tollenaar, C Seynaeve, JD Figueroa, M Garcia-Closas, L Brinton, J Lissowska, MJ Hooning, A Hollestelle, RA Oldenburg, AMW van den Ouweland, A Cox, MWR Reed, M Shah, A Jakubowska, J Lubinski, K Jaworska, K Durda, M Jones, M Schoemaker, A Ashworth, A Swerdlow, J Beesley, X Chen, kConFab Investigators, Australian Ovarian Cancer Study Group, KR Muir, A Lophatananon, S Rattanamongkongul, A Chaiwerawattana, D Kang, K-Y Yoo, D-Y Noh, C-Y Shen, J-C Yu, P-E Wu, C-N Hsiung, A Perkins, R Swann, L Velentzis, DM Eccles, WJ Tapper, SM Gerty, NJ Graham, BAJ Ponder, G Chenevix-Trench, PDP Pharoah, M Lathrop, AM Dunning, N Rahman, J Peto, DF Easton
Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ∼70,000 cases and ∼68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.