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Garcia-Closas, M.* ; Couch, F.J.* ; Lindström, S.* ; Michailidouo, K.* ; Schmidt, M.K.* ; Brook, M.N.* ; Orr, N.* ; Rhie, S.K.* ; Riboli, E.* ; Feigelson, H.S.* ; Le Marchand, L.* ; Buring, J.E.* ; Eccles, D.* ; Miron, P.* ; Fasching, P.A.* ; Brauch, H.* ; Chang-Claude, J.* ; Carpenter, J.* ; Godwin, A.K.* ; Nevanlinna, H.* ; Giles, G.G.* ; Cox, A.* ; Hopper, J.L.* ; Bolla, M.K.* ; Wang, Q.* ; Dennis, J.* ; Dicks, E.* ; Howat, W.J.* ; Schoof, N.* ; Bojesen, S.E.* ; Lambrechts, D.* ; Broeks, A.* ; Andrulis, I.L.* ; Guénel, P.* ; Burwinkel, B.* ; Sawyer, E.J.* ; Hollestelle, A.* ; Fletcher, O.* ; Winqvist, R.* ; Brenner, H.* ; Mannermaa, A.* ; Hamann, U.* ; Meindl, A.* ; Lindblom, A.* ; Zheng, W.* ; Devillee, P.* ; Goldberg, M.S.* ; Lubinski, J.* ; Kristensen, V.* ; Swerdlow, A.* ; Anton-Culver, H.* ; Doerk, T.* ; Muir, K.* ; Matsuo, K.* ; Wu, A.H.* ; Radice, P.* ; Teo, S.H.* ; Shu, X.O.* ; Blot, W.* ; Kang, D.* ; Hartman, M.* ; Sangrajrang, S.* ; Shen, C.Y.* ; Southey, M.C.* ; Park, D.J.* ; Hammet, F.* ; Stone, J.* ; van't Veer, L.J.* ; Rutgers, E.J.* ; Lophatananon, A.* ; Stewart-Brown, S.* ; Siriwanarangsan, P.* ; Peto, J.* ; Schrauder, M.G.* ; Ekici, A.B.* ; Beckmann, M.W.* ; Silva, I.D.* ; Johnson, N.* ; Warren, H.* ; Tomlins, I.* ; Kerin, M.J.* ; Miller, N.* ; Marme, F.* ; Schneeweiss, A.* ; Sohn, C.* ; Truong, T.* ; Laurent-Puig, P.* ; Kerbrat, P.* ; Nørdestgaard, B.G.* ; Nielsen, S.F.* ; Flyger, H.* ; Milne, R.L.* ; Perez, J.I.A.* ; Menendez, P.* ; Müller, H.* ; Arndt, V.* ; Stegmaier, C.* ; Lichtner, P. ; Lochmann, M.* ; Justenhoven, C.* ; Ko, Y.D.* ; Muranen, T.A.* ; Aittomäki, K.* ; Blomqvist, C.* ; Greco, D.* ; Heikkinen, T.* ; Ito, H.* ; Iwata, H.* ; Yatabe, Y.* ; Antonenkova, N.N.* ; Margolin, S.* ; Kataja, V.* ; Kosma, V.M.* ; Hartikainen, J.M.* ; Balleine, R.* ; Tseng, C.C.* ; van Den Berg, D.* ; Stram, D.O.* ; Neven, P.* ; Dieudonne, A.S.* ; Leunen, K.* ; Rudolph, A.* ; Nickels, S.* ; Flesch-Janys, D.* ; Peterlongo, P.* ; Peissel, B.* ; Bernard, L.* ; Olson, J.E.* ; Wang, X.S.* ; Stevens, K.* ; Severi, G.* ; Baglietto, L.* ; McLean, C.* ; Coetzee, G.A.* ; Feng, Y.* ; Henderson, B.E.* ; Schumacher, F.* ; Bogdanova, N.V.* ; Labreche, F.* ; Dumont, M.* ; Yip, C.H.* ; Taib, N.A.M.* ; Cheng, C.Y.* ; Shrubsole, M.* ; Long, J.R.* ; Pylkäs, K.* ; Jukkola-Vuorinen, A.* ; Kauppila, S.* ; Knight, J.A.* ; Glendon, G.* ; Mulligan, A.M.* ; Tollenaar, R.A.E.M.* ; Seynaeve, C.M.* ; Kriege, M.* ; Hooning, M.J.* ; van den Ouweland, A.M.W.* ; van Deurzen, C.H.M.* ; Lu, W.* ; Gao, Y.T.* ; Cai, H.* ; Balasubramanian, S.P.* ; Cross, S.S.* ; Reed, M.W.R.* ; Signorello, L.* ; Cai, Q.Y.* ; Shah, M.* ; Miao, H.* ; Chan, C.W.* ; Chia, K.S.* ; Jakubowska, A.* ; Jaworska, K.* ; Durda, K.* ; Hsiung, C.N.* ; Wu, P.* ; Yu, J.C.* ; Ashworth, A.* ; Jones, M.* ; Tessier, D.C.* ; González-Neira, A.* ; Pita, G.* ; Alonso, M.R.* ; Vincent, D.* ; Bacot, F.* ; Ambrosone, C.B.* ; Bandera, E.V.* ; John, E.M.* ; Chen, G.K.* ; Hu, J.J.* ; Rodriguez-Gil, J.L.* ; Bernstein, L.* ; Press, M.F.* ; Ziegler, R.G.* ; Millikan, R.M.* ; Deming-Halverson, S.L.* ; Nyante, S.* ; Ingles, S.A.* ; Waisfisz, Q.* ; Tsimiklis, H.* ; Makalic, E.* ; Schmidt, D.* ; Bui, M.* ; Gibson, L.* ; Müller-Myhsok, B.* ; Schmutzler, R.K.* ; Hein, R.* ; Dahmen, N.* ; Beckmann, L.* ; Aaltonen, K.* ; Czene, K.* ; Irwanto, A.* ; Liu, J.J.* ; Turnbull, C.* ; Rahman, N.* ; Meijers-Heijboer, H.* ; Uitterlinden, A.G.* ; Rivadeneira, F.* ; Olswold, C.* ; Slager, S.* ; Pilarski, R.* ; Ademuyiwa, F.* ; Konstantopoulou, I.* ; Martin, N.G.* ; Montgomery, G.W.* ; Slamon, D.J.* ; Rauh, C.* ; Lux, M.P.* ; Jud, S.M.* ; Brüning, T* ; Weaver, J.* ; Harma, P.* ; Pathak, H.* ; Tapper, W.* ; Gerty, S.* ; Durcan, L.* ; Trichopoulos, D.* ; Tumino, R.* ; Peeters, P.H.* ; Kaaks, R.* ; Campa, D.* ; Canzian, F.* ; Weiderpass, E.* ; Johansson, M.* ; Khaw, K.T.* ; Travis, R.* ; Clavel-Chapelon, F.* ; Kolonel, L.N.* ; Chen, C.* ; Beck, A.* ; Hankinson, S.E.* ; Berg, C.D.* ; Hoover, R.N.* ; Lissowska, J.* ; Figueroa, J.D.* ; Chasman, D.I.* ; Gaudet, M.M.* ; Diver, W.R.* ; Willett, W.C.* ; Hunter, D.J.* ; Simard, J.* ; Benítez, J.* ; Dunning, A.M.* ; Sherman, M.E.* ; Chenevix-Trench, G.* ; Chanock, S.J.* ; Hall, P.* ; Pharoah, P.D.P.* ; Vachon, C.* ; Easton, D.F.* ; Haiman, C.A.* ; Kraft, P.*

Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

Nat. Genet. 45, 392-398 (2013)

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Open Access Green as soon as Postprint is submitted to ZB.

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Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a metaanalysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P= 2.1 x 10(-12) and LGR6, P = 1.4 x 10(-8)), 2p24.1 (P = 4.6 x 10(-8)) and 16q12.2 (FTO, P = 4.0 x 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P> 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

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