Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

Maya Ghoussaini, Stacey L. Edwards, Kyriaki Michailidou, Silje Nord, Richard Cowper-Sal·lari, Kinjal Desai, Siddhartha Kar, Kristine M. Hillman, Susanne Kaufmann, Dylan M. Glubb, Jonathan Beesley, Joe Dennis, Manjeet K. Bolla, Qin Wang, Ed Dicks, Qi Guo, Marjanka K. Schmidt, Mitul Shah, Robert Luben, Judith Brown, Kamila Czene, Hatef Darabi, Mikael Eriksson, Daniel Klevebring, Stig E. Bojesen, Børge G. Nordestgaard, Sune F. Nielsen, Henrik Flyger, Diether Lambrechts, Bernard Thienpont, Patrick Neven, Hans Wildiers, Annegien Broeks, Laura J. Van’t Veer, Emiel J. Th Rutgers, Fergus J. Couch, Janet E. Olson, Emily Hallberg, Celine Vachon, Jenny Chang-Claude, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Julian Peto, Isabel dos-Santos-Silva, Lorna Gibson, Heli Nevanlinna, Taru A. Muranen, Kristiina Aittomäki, Carl Blomqvist, Per Hall, Jingmei Li, Jianjun Liu, Keith Humphreys, Daehee Kang, Ji-Yeob Choi, Sue K. Park, Dong-Young Noh, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Yasushi Yatabe, Pascal Guénel, Thérèse Truong, Florence Menegaux, Marie Sanchez, Barbara Burwinkel, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Anna H. Wu, Chiu-chen Tseng, David Van Den Berg, Daniel O. Stram, Javier Benitez, M. Pilar Zamora, Jose Ignacio Arias Perez, Primitiva Menéndez, Xiao-Ou Shu, Wei Lu, Yu-Tang Gao, Qiuyin Cai, Angela Cox, Simon S. Cross, Malcolm W. R. Reed, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Sandrine Tchatchou, Elinor J. Sawyer, Ian Tomlinson, Michael J. Kerin, Nicola Miller, Christopher A. Haiman, Brian E. Henderson, Fredrick Schumacher, Loic Le Marchand, Annika Lindblom, Sara Margolin, Soo Hwang TEO, Cheng Har YIP, Daphne S. C. Lee, Tien Y. Wong, Maartje J. Hooning, John W. M. Martens, J. Margriet Collée, Carolien H. M. van Deurzen, John L. Hopper, Melissa C. Southey, Helen Tsimiklis, Miroslav K. Kapuscinski, Chen-Yang Shen, Pei-Ei Wu, Jyh-Cherng Yu, Shou-Tung Chen, Grethe Grenaker Alnæs, Anne-Lise Borresen-Dale, Graham G. Giles, Roger L. Milne, Catriona McLean, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Mikael Hartman, Hui Miao, Ahmad Bin Syed Buhari, Yik Ying Teo, Peter A. Fasching, Lothar Haeberle, Arif B. Ekici, Matthias W. Beckmann, Hermann Brenner, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Anthony Swerdlow, Alan Ashworth, Nick Orr, Minouk J. Schoemaker, Montserrat García-Closas, Jonine Figueroa, Stephen J. Chanock, Jolanta Lissowska, Jacques Simard, Mark S. Goldberg, France Labrèche, Martine Dumont, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Hiltrud Brauch, Thomas Brüning, Yon-Dschun Koto, Paolo Radice, Paolo Peterlongo, Bernardo Bonanni, Sara Volorio, Thilo Dörk, Natalia V. Bogdanova, Sonja Helbig, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M. Hartikainen, Peter Devilee, Robert A. E. M. Tollenaar, Caroline Seynaeve, Christi J. Van Asperen, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Susan Slager, Amanda E. Toland, Christine B. Ambrosone, Drakoulis Yannoukakos, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Ute Hamann, Diana Torres, Wei Zheng, Jirong Long, Hoda Anton-Culver, Susan L. Neuhausen, Craig Luccarini, Caroline Baynes, Shahana Ahmed, Mel Maranian, Catherine S. Healey, Anna González-Neira, Guillermo Pita, M. Rosario Alonso, Nuria Álvarez, Daniel Herrero, Daniel C. Tessier, Daniel Vincent, Francois Bacot, Ines de Santiago, Jason Carroll, Carlos Caldas, Melissa A. Brown, Mathieu Lupien, Vessela N. Kristensen, Paul D P Pharoah, Georgia Chenevix-Trench, Juliet D French, Douglas F. Easton, Alison M. Dunning, Australian Ovarian Cancer Management Group, Penny Webb, David Bowtell, Anna De Fazio

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. More... »

PAGES

4999

Journal

TITLE

Nature Communications

ISSUE

1

VOLUME

5

Author Affiliations

  • University of Cambridge
  • University of Queensland
  • Oslo University Hospital
  • Princess Margaret Cancer Centre
  • Dartmouth College
  • QIMR Berghofer Medical Research Institute
  • Antoni van Leeuwenhoek Hospital
  • Karolinska Institute
  • University of Copenhagen
  • Herlev Hospital
  • Flanders Institute for Biotechnology
  • KU Leuven
  • Universitaire Ziekenhuizen Leuven
  • Mayo Clinic
  • German Cancer Research Center
  • University Medical Center Hamburg-Eppendorf
  • London School of Hygiene & Tropical Medicine
  • Helsinki University Central Hospital
  • Genome Institute of Singapore
  • Seoul National University
  • Kyushu University
  • Aichi Cancer Center
  • University of Paris-Sud
  • Heidelberg University
  • University of Southern California
  • Spanish National Cancer Research Centre
  • Hospital Universitario La Paz
  • Hospital Monte Naranco
  • Shanghai Cancer Institute
  • University of Sheffield
  • University of Toronto
  • Mount Sinai Hospital
  • Lunenfeld-Tanenbaum Research Institute
  • King's College London
  • Wellcome Centre for Human Genetics
  • University Hospital Galway
  • University of Hawaii at Manoa
  • University Malaya Medical Centre
  • National University of Singapore
  • Erasmus University Medical Center
  • University of Melbourne
  • Institute of Biomedical Sciences, Academia Sinica
  • Academia Sinica
  • Tri-Service General Hospital
  • University of Oslo
  • Cancer Council Victoria
  • Alfred Hospital
  • University of Manchester
  • University of Warwick
  • Ministry of Public Health
  • National University Health System
  • University of California Los Angeles
  • Krebsregister Saarland
  • Institute of Cancer Research
  • National Cancer Institute
  • Centrum Onkologii Instytut
  • Université Laval
  • Royal Victoria Hospital
  • University of Montreal
  • University of Oulu
  • Ruhr University Bochum
  • Istituto Nazionale dei Tumori
  • FIRC Institute of Molecular Oncology
  • European Institute of Oncology
  • Hannover Medical School
  • University of Eastern Finland
  • Leiden University Medical Center
  • Pomeranian Medical University
  • The Ohio State University
  • Roswell Park Cancer Institute
  • National Centre of Scientific Research Demokritos
  • National Cancer Institute of Thailand
  • International Agency For Research On Cancer
  • Pontifical Xavierian University
  • University of California, Irvine
  • City Of Hope National Medical Center
  • McGill University and Génome Québec Innovation Centre
  • McGill University
  • Peter MacCallum Cancer Centre
  • Westmead Hospital
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms5999

    DOI

    http://dx.doi.org/10.1038/ncomms5999

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1044808072

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25248036


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