Genome-wide association studies identify four ER negative-specific breast cancer risk loci.
; Schrauder, MG; Ekici, AB; Beckmann, MW; Dos Santos Silva, I; Johnson, N; Warren, H; Tomlinson, I; Kerin, MJ; Miller, N; Marme, F; Schneeweiss, A; Sohn, C; Truong, T; Laurent-Puig, P; Kerbrat, P; Nordestgaard, BG; Nielsen, SF; Flyger, H; Milne, RL; Perez, JIA; Menéndez, P; Müller, H; Arndt, V; Stegmaier, C; Lichtner, P; Lochmann, M; Justenhoven, C; Ko, Y; Gene ENvironmental Interaction and breast CAncer (GENICA) Networ; Muranen, TA; Aittomäki, K; Blomqvist, C; Greco, D; Heikkinen, T; Ito, H; Iwata, H; Yatabe, Y; Antonenkova, NN; Margolin, S; Kataja, V; Kosma, V; Hartikainen, JM; Balleine, R; kConFab Investigators; Tseng, C; Berg, DVD; Stram, DO; Neven, P; Dieudonné, A; Leunen, K; Rudolph, A; Nickels, S; Flesch-Janys, D; Peterlongo, P; Peissel, B; Bernard, L; Olson, JE; Wang, X; Stevens, K; Severi, G; Baglietto, L; McLean, C; Coetzee, GA; Feng, Y; Henderson, BE; Schumacher, F; Bogdanova, NV; Labrèche, F; Dumont, M; Yip, CH; Taib, NAM; Cheng, C; Shrubsole, M; Long, J; Pylkäs, K; Jukkola-Vuorinen, A; Kauppila, S; Knight, JA; Glendon, G; Mulligan, AM; Tollenaar, RA; Seynaeve, CM; Kriege, M; Hooning, MJ; van den Ouweland, AM; van Deurzen, CH; Lu, W; Gao, Y; Cai, H; Balasubramanian, SP; Cross, SS; Reed, MW; Signorello, L; Cai, Q; Shah, M; Miao, H; Chan, CW; Chia, KS; Jakubowska, A; Jaworska, K; Durda, K; Hsiung, C; Wu, P; Yu, J; Ashworth, A; Jones, M; Tessier, DC; González-Neira, A; Pita, G; Alonso, MR; Vincent, D; Bacot, F; Ambrosone, CB; Bandera, EV; John, EM; Chen, GK; Hu, JJ; Rodriguez-Gil, JL; Bernstein, L; Press, MF; Ziegler, RG; Millikan, RM; Deming-Halverson, SL; Nyante, S; Ingles, SA; Waisfisz, Q; Tsimiklis, H; Makalic, E; Schmidt, D; Bui, M; Gibson, L; Müller-Myhsok, B; Schmutzler, RK; Hein, R; Dahmen, N; Beckmann, L; Aaltonen, K; Czene, K; Irwanto, A; Liu, J; Turnbull, C; Familial Breast Cancer Study (FBCS); Rahman, N; Meijers-Heijboer, H; Uitterlinden, AG; Rivadeneira, F; Australian Breast Cancer Tissue Bank (ABCTB) Investigators; Olswold, C; Slager, S; Pilarski, R; Ademuyiwa, F; Konstantopoulou, I; Martin, NG; Montgomery, GW; Slamon, DJ; Rauh, C; Lux, MP; Jud, SM; Bruning, T; Weaver, J; Sharma, P; Pathak, H; Tapper, W; Gerty, S; Durcan, L; Trichopoulos, D; Tumino, R; Peeters, PH; Kaaks, R; Campa, D; Canzian, F; Weiderpass, E; Johansson, M; Khaw, K; Travis, R; Clavel-Chapelon, F; Kolonel, LN; Chen, C; Beck, A; Hankinson, SE; Berg, CD; Hoover, RN; Lissowska, J; Figueroa, JD; Chasman, DI; Gaudet, MM; Diver, WR; Willett, WC; Hunter, DJ; Simard, J; Benitez, J; Dunning, AM; Sherman, ME; Chenevix-Trench, G; Chanock, SJ; Hall, P; Pharoah, PD; Vachon, C; Easton, DF; Haiman, CA; Kraft, P and
(2013)
Genome-wide association studies identify four ER negative-specific breast cancer risk loci.
Nature genetics, 45 (4).
392-398e2.
ISSN 1061-4036
DOI: 10.1038/ng.2561
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 meta-analysis 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 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 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.