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Title: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation
Authors: 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, Qianfen
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 W R
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 S C
Wong, Tien Y
Hooning, Maartje J
Martens, John W M
Collée, J Margriet
van Deurzen, Carolien H M
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 A E M
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 D P
Chenevix-Trench, Georgia
French, Juliet D
Easton, Douglas F
Dunning, Alison M
Australian Ovarian Cancer Management Group
Australian Ovarian Cancer Management Group #
Issue Date: 23-Sep-2014
Series Title: Nature communications vol:4 pages:4999
Article number: 10.1038/ncomms5999
Abstract: 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.
URI: 
ISSN: 2041-1723
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Oncology
Laboratory of Translational Genetics (Vesalius Research Center) (+)
Gynaecological Oncology
× corresponding author
# (joint) last author

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