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

M Garcia-Closas, F J Couch, S Lindstrom, K Michailidou, M K Schmidt, M N Brook, N Orr, S K Rhie, E Riboli, H S Feigelson, L Le Marchand, J E Buring, D Eccles, P Miron, P A Fasching, H Brauch, J Chang-Claude, J Carpenter, A K Godwin, H NevanlinnaG G Giles, A Cox, J L Hopper, M K Bolla, Q Wang, J Dennis, E Dicks, W J Howat, N Schoof, S E Bojesen, D Lambrechts, A Broeks, I L Andrulis, P Guenel, B Burwinkel, E J Sawyer, A Hollestelle, O Fletcher, R Winqvist, H Brenner, A Mannermaa, U Hamann, A Meindl, A Lindblom, W Zheng, P Devillee, M S Goldberg, J Lubinski, V Kristensen, A Swerdlow, H Anton-Culver, T Dork, K Muir, K Matsuo, A H Wu, P Radice, S H Teo, X O Shu, W Blot, D Kang, M Hartman, S Sangrajrang, C Y Shen, M C Southey, D J Park, F Hammet, J Stone, L J Veer, E J Rutgers, A Lophatananon, S Stewart-Brown, P Siriwanarangsan, J Peto, M G Schrauder, A B Ekici, M W Beckmann, I Dos Santos Silva, N Johnson, H Warren, I Tomlinson, M J Kerin, N Miller, F Marme, A Schneeweiss, C Sohn, T Truong, P Laurent-Puig, P Kerbrat, B G Nordestgaard, S F Nielsen, H Flyger, R L Milne, J I Perez, P Menendez, H Muller, V Arndt, C Stegmaier, P Lichtner, M Lochmann, C Justenhoven, Y D Ko, T A Muranen, K Aittomaki, C Blomqvist, D Greco, T Heikkinen, H Ito, H Iwata, Y Yatabe, N N Antonenkova, S Margolin, V Kataja, V M Kosma, J M Hartikainen, R Balleine, C C Tseng, D V Berg, D O Stram, P Neven, A S Dieudonne, K Leunen, A Rudolph, S Nickels, D Flesch-Janys, P Peterlongo, B Peissel, L Bernard, J E Olson, X Wang, K Stevens, G Severi, L Baglietto, C McLean, G A Coetzee, Y Feng, B E Henderson, F Schumacher, N V Bogdanova, F Labreche, M Dumont, C H Yip, N A Taib, C Y Cheng, M Shrubsole, J Long, K Pylkas, A Jukkola-Vuorinen, S Kauppila, J A Knight, G Glendon, A M Mulligan, R A Tollenaar, C M Seynaeve, M Kriege, M J Hooning, A M van den Ouweland, C H van Deurzen, W Lu, Y T Gao, H Cai, S P Balasubramanian, S S Cross, M W Reed, L Signorello, Q Cai, M Shah, H Miao, C W Chan, K S Chia, A Jakubowska, K Jaworska, K Durda, C N Hsiung, P E Wu, J C Yu, A Ashworth, M Jones, D C Tessier, A Gonzalez-Neira, G Pita, M R Alonso, D Vincent, F Bacot, C B Ambrosone, E V Bandera, E M John, G K Chen, J J Hu, J L Rodriguez-Gil, L Bernstein, M F Press, R G Ziegler, R M Millikan, S L Deming-Halverson, S Nyante, S A Ingles, Q Waisfisz, H Tsimiklis, E Makalic, D Schmidt, M Bui, L Gibson, B Muller-Myhsok, R K Schmutzler, R Hein, N Dahmen, L Beckmann, K Aaltonen, K Czene, A Irwanto, J Liu, C Turnbull, N Rahman, H Meijers-Heijboer, A G Uitterlinden, F Rivadeneira, C Olswold, S Slager, R Pilarski, F Ademuyiwa, I Konstantopoulou, N G Martin, G W Montgomery, D J Slamon, C Rauh, M P Lux, S M Jud, T Bruning, J Weaver, P Sharma, H Pathak, W Tapper, S Gerty, L Durcan, D Trichopoulos, R Tumino, P H Peeters, R Kaaks, D Campa, F Canzian, E Weiderpass, M Johansson, K T Khaw, R Travis, F Clavel-Chapelon, L N Kolonel, C Chen, A Beck, S E Hankinson, C D Berg, R N Hoover, J Lissowska, J D Figueroa, D I Chasman, M M Gaudet, W R Diver, W C Willett, D J Hunter, J Simard, J Benitez, A M Dunning, M E Sherman, G Chenevix-Trench, S J Chanock, P Hall, P D Pharoah, C Vachon, D F Easton, C A Haiman, P Kraft

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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 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.
    Original languageEnglish
    Pages (from-to)392-8
    Number of pages383
    JournalNat Genet
    Volume45
    Issue number4
    DOIs
    Publication statusPublished - 2013

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