- Main
Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.
- Author(s): Ghoussaini, Maya;
- Edwards, Stacey L;
- Michailidou, Kyriaki;
- Nord, Silje;
- Cowper-Sal Lari, Richard;
- Desai, Kinjal;
- Kar, Siddhartha;
- Hillman, Kristine M;
- Kaufmann, Susanne;
- Glubb, Dylan M;
- Beesley, Jonathan;
- Dennis, Joe;
- Bolla, Manjeet K;
- Wang, Qin;
- Dicks, Ed;
- Guo, Qi;
- Schmidt, Marjanka K;
- Shah, Mitul;
- Luben, Robert;
- Brown, Judith;
- Czene, Kamila;
- Darabi, Hatef;
- Eriksson, Mikael;
- Klevebring, Daniel;
- Bojesen, Stig E;
- Nordestgaard, Børge G;
- Nielsen, Sune F;
- Flyger, Henrik;
- Lambrechts, Diether;
- Thienpont, Bernard;
- Neven, Patrick;
- Wildiers, Hans;
- Broeks, Annegien;
- Van't Veer, Laura J;
- Th Rutgers, Emiel J;
- Couch, Fergus J;
- Olson, Janet E;
- Hallberg, Emily;
- Vachon, Celine;
- Chang-Claude, Jenny;
- Rudolph, Anja;
- Seibold, Petra;
- Flesch-Janys, Dieter;
- Peto, Julian;
- Dos-Santos-Silva, Isabel;
- Gibson, Lorna;
- Nevanlinna, Heli;
- Muranen, Taru A;
- Aittomäki, Kristiina;
- Blomqvist, Carl;
- Hall, Per;
- Li, Jingmei;
- Liu, Jianjun;
- Humphreys, Keith;
- Kang, Daehee;
- Choi, Ji-Yeob;
- Park, Sue K;
- Noh, Dong-Young;
- Matsuo, Keitaro;
- Ito, Hidemi;
- Iwata, Hiroji;
- Yatabe, Yasushi;
- Guénel, Pascal;
- Truong, Thérèse;
- Menegaux, Florence;
- Sanchez, Marie;
- Burwinkel, Barbara;
- Marme, Frederik;
- Schneeweiss, Andreas;
- Sohn, Christof;
- Wu, Anna H;
- Tseng, Chiu-Chen;
- Van Den Berg, David;
- Stram, Daniel O;
- Benitez, Javier;
- Zamora, M Pilar;
- Perez, Jose Ignacio Arias;
- Menéndez, Primitiva;
- Shu, Xiao-Ou;
- Lu, Wei;
- Gao, Yu-Tang;
- Cai, Qiuyin;
- Cox, Angela;
- Cross, Simon S;
- Reed, Malcolm WR;
- Andrulis, Irene L;
- Knight, Julia A;
- Glendon, Gord;
- Tchatchou, Sandrine;
- Sawyer, Elinor J;
- Tomlinson, Ian;
- Kerin, Michael J;
- Miller, Nicola;
- Haiman, Christopher A;
- Henderson, Brian E;
- Schumacher, Fredrick;
- Le Marchand, Loic;
- Lindblom, Annika;
- Margolin, Sara;
- Teo, Soo Hwang;
- Yip, Cheng Har;
- Lee, Daphne SC;
- Wong, Tien Y;
- Hooning, Maartje J;
- Martens, John WM;
- Collée, J Margriet;
- van Deurzen, Carolien HM;
- Hopper, John L;
- Southey, Melissa C;
- Tsimiklis, Helen;
- Kapuscinski, Miroslav K;
- Shen, Chen-Yang;
- Wu, Pei-Ei;
- Yu, Jyh-Cherng;
- Chen, Shou-Tung;
- Alnæs, Grethe Grenaker;
- Borresen-Dale, Anne-Lise;
- Giles, Graham G;
- Milne, Roger L;
- McLean, Catriona;
- Muir, Kenneth;
- Lophatananon, Artitaya;
- Stewart-Brown, Sarah;
- Siriwanarangsan, Pornthep;
- Hartman, Mikael;
- Miao, Hui;
- Buhari, Shaik Ahmad Bin Syed;
- Teo, Yik Ying;
- Fasching, Peter A;
- Haeberle, Lothar;
- Ekici, Arif B;
- Beckmann, Matthias W;
- Brenner, Hermann;
- Dieffenbach, Aida Karina;
- Arndt, Volker;
- Stegmaier, Christa;
- Swerdlow, Anthony;
- Ashworth, Alan;
- Orr, Nick;
- Schoemaker, Minouk J;
- García-Closas, Montserrat;
- Figueroa, Jonine;
- Chanock, Stephen J;
- Lissowska, Jolanta;
- Simard, Jacques;
- Goldberg, Mark S;
- Labrèche, France;
- Dumont, Martine;
- Winqvist, Robert;
- Pylkäs, Katri;
- Jukkola-Vuorinen, Arja;
- Brauch, Hiltrud;
- Brüning, Thomas;
- Koto, Yon-Dschun;
- Radice, Paolo;
- Peterlongo, Paolo;
- Bonanni, Bernardo;
- Volorio, Sara;
- Dörk, Thilo;
- Bogdanova, Natalia V;
- Helbig, Sonja;
- Mannermaa, Arto;
- Kataja, Vesa;
- Kosma, Veli-Matti;
- Hartikainen, Jaana M;
- Devilee, Peter;
- Tollenaar, Robert AEM;
- Seynaeve, Caroline;
- Van Asperen, Christi J;
- Jakubowska, Anna;
- Lubinski, Jan;
- Jaworska-Bieniek, Katarzyna;
- Durda, Katarzyna;
- Slager, Susan;
- Toland, Amanda E;
- Ambrosone, Christine B;
- Yannoukakos, Drakoulis;
- Sangrajrang, Suleeporn;
- Gaborieau, Valerie;
- Brennan, Paul;
- McKay, James;
- Hamann, Ute;
- Torres, Diana;
- Zheng, Wei;
- Long, Jirong;
- Anton-Culver, Hoda;
- Neuhausen, Susan L;
- Luccarini, Craig;
- Baynes, Caroline;
- Ahmed, Shahana;
- Maranian, Mel;
- Healey, Catherine S;
- González-Neira, Anna;
- Pita, Guillermo;
- Alonso, M Rosario;
- Alvarez, Nuria;
- Herrero, Daniel;
- Tessier, Daniel C;
- Vincent, Daniel;
- Bacot, Francois;
- de Santiago, Ines;
- Carroll, Jason;
- Caldas, Carlos;
- Brown, Melissa A;
- Lupien, Mathieu;
- Kristensen, Vessela N;
- Pharoah, Paul DP;
- Chenevix-Trench, Georgia;
- French, Juliet D;
- Easton, Douglas F;
- Dunning, Alison M;
- Australian Ovarian Cancer Management Group;
- Australian Ovarian Cancer Management Group
- et al.
Published Web Location
https://doi.org/10.1038/ncomms5999Abstract
GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.
Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
Main Content
Enter the password to open this PDF file:
-
-
-
-
-
-
-
-
-
-
-
-
-
-