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

Author

Listed:
  • Maya Ghoussaini

    (Centre for Cancer Genetic Epidemiology)

  • Stacey L. Edwards

    (QIMR Berghofer Medical Research Institute
    School of Chemistry and Molecular Biosciences, The University of Queensland)

  • Kyriaki Michailidou

    (Centre for Cancer Genetic Epidemiology, University of Cambridge)

  • Silje Nord

    (Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet)

  • Richard Cowper-Sal·lari

    (The Princess Margaret Cancer Centre, University Health Network)

  • Kinjal Desai

    (The Princess Margaret Cancer Centre, University Health Network
    Geisel School of Medicine, Dartmouth College)

  • Siddhartha Kar

    (Centre for Cancer Genetic Epidemiology, University of Cambridge)

  • Kristine M. Hillman

    (QIMR Berghofer Medical Research Institute
    School of Chemistry and Molecular Biosciences, The University of Queensland)

  • Susanne Kaufmann

    (QIMR Berghofer Medical Research Institute
    School of Chemistry and Molecular Biosciences, The University of Queensland)

  • Dylan M. Glubb

    (QIMR Berghofer Medical Research Institute)

  • Jonathan Beesley

    (QIMR Berghofer Medical Research Institute)

  • Joe Dennis

    (Centre for Cancer Genetic Epidemiology, University of Cambridge)

  • Manjeet K. Bolla

    (Centre for Cancer Genetic Epidemiology, University of Cambridge)

  • Qin Wang

    (Centre for Cancer Genetic Epidemiology, University of Cambridge)

  • Ed Dicks

    (Centre for Cancer Genetic Epidemiology)

  • Qi Guo

    (Centre for Cancer Genetic Epidemiology)

  • Marjanka K. Schmidt

    (Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital)

  • Mitul Shah

    (Centre for Cancer Genetic Epidemiology)

  • Robert Luben

    (Centre for Cancer Genetic Epidemiology, University of Cambridge)

  • Judith Brown

    (Centre for Cancer Genetic Epidemiology, University of Cambridge)

  • Kamila Czene

    (Karolinska Institutet)

  • Hatef Darabi

    (Karolinska Institutet)

  • Mikael Eriksson

    (Karolinska Institutet)

  • Daniel Klevebring

    (Karolinska Institutet)

  • Stig E. Bojesen

    (Copenhagen General Population Study, Herlev Hospital
    Herlev Hospital Copenhagen University Hospital
    Faculty of Health and Medical Sciences, University of Copenhagen)

  • Børge G. Nordestgaard

    (Copenhagen General Population Study, Herlev Hospital
    Herlev Hospital Copenhagen University Hospital
    Faculty of Health and Medical Sciences, University of Copenhagen)

  • Sune F. Nielsen

    (Copenhagen General Population Study, Herlev Hospital
    Herlev Hospital Copenhagen University Hospital)

  • Henrik Flyger

    (Herlev Hospital, Copenhagen University Hospital)

  • Diether Lambrechts

    (Laboratory for Translational Genetics
    Vesalius Research Center (VRC), VIB)

  • Bernard Thienpont

    (Vesalius Research Center (VRC), VIB
    Vesalius Research Center, University of Leuven)

  • Patrick Neven

    (University of Leuven
    Multidisciplinary Breast Center, University Hospitals Leuven)

  • Hans Wildiers

    (University of Leuven
    Multidisciplinary Breast Center, University Hospitals Leuven)

  • Annegien Broeks

    (Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital)

  • Laura J. Van’t Veer

    (Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital)

  • Emiel J. Th Rutgers

    (Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital)

  • Fergus J. Couch

    (Mayo Clinic)

  • Janet E. Olson

    (Mayo Clinic)

  • Emily Hallberg

    (Mayo Clinic)

  • Celine Vachon

    (Mayo Clinic)

  • Jenny Chang-Claude

    (German Cancer Research Center (DKFZ))

  • Anja Rudolph

    (German Cancer Research Center (DKFZ))

  • Petra Seibold

    (German Cancer Research Center (DKFZ))

  • Dieter Flesch-Janys

    (University Clinic Hamburg-Eppendorf)

  • Julian Peto

    (London School of Hygiene and Tropical Medicine)

  • Isabel dos-Santos-Silva

    (London School of Hygiene and Tropical Medicine)

  • Lorna Gibson

    (London School of Hygiene and Tropical Medicine)

  • Heli Nevanlinna

    (Helsinki University Central Hospital)

  • Taru A. Muranen

    (Helsinki University Central Hospital)

  • Kristiina Aittomäki

    (University of Helsinki Helsinki University Central Hospital)

  • Carl Blomqvist

    (University of Helsinki, Helsinki University Central Hospital)

  • Per Hall

    (Karolinska Institutet)

  • Jingmei Li

    (Genome Institute of Singapore)

  • Jianjun Liu

    (Genome Institute of Singapore)

  • Keith Humphreys

    (Karolinska Institutet)

  • Daehee Kang

    (Cancer Research Institute, Seoul National University College of Medicine
    Seoul National University Graduate School
    Seoul National University College of Medicine)

  • Ji-Yeob Choi

    (Cancer Research Institute, Seoul National University College of Medicine
    Seoul National University Graduate School)

  • Sue K. Park

    (Cancer Research Institute, Seoul National University College of Medicine
    Seoul National University Graduate School
    Seoul National University College of Medicine)

  • Dong-Young Noh

    (Seoul National University College of Medicine)

  • Keitaro Matsuo

    (Kyushu University Faculty of Medical Sciences)

  • Hidemi Ito

    (Aichi Cancer Center Research Institute)

  • Hiroji Iwata

    (Aichi Cancer Center Hospital)

  • Yasushi Yatabe

    (Aichi Cancer Center Hospital)

  • Pascal Guénel

    (Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer
    University Paris-Sud, UMRS 1018)

  • Thérèse Truong

    (Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer
    University Paris-Sud, UMRS 1018)

  • Florence Menegaux

    (Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer
    University Paris-Sud, UMRS 1018)

  • Marie Sanchez

    (Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer
    University Paris-Sud, UMRS 1018)

  • Barbara Burwinkel

    (University of Heidelberg
    Molecular Epidemiology Group, German Cancer Research Center (DKFZ))

  • Frederik Marme

    (University of Heidelberg
    National Center for Tumor Diseases, University of Heidelberg)

  • Andreas Schneeweiss

    (University of Heidelberg
    National Center for Tumor Diseases, University of Heidelberg)

  • Christof Sohn

    (University of Heidelberg)

  • Anna H. Wu

    (Keck School of Medicine University of Southern California)

  • Chiu-chen Tseng

    (Keck School of Medicine University of Southern California)

  • David Van Den Berg

    (Keck School of Medicine University of Southern California)

  • Daniel O. Stram

    (Keck School of Medicine University of Southern California)

  • Javier Benitez

    (Centro de Investigación en Red de Enfermedades Raras (CIBERER)
    Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO))

  • M. Pilar Zamora

    (Servicio de Oncología Médica, Hospital Universitario La Paz)

  • Jose Ignacio Arias Perez

    (Servicio de Cirugía General y Especialidades, Hospital Monte Naranco)

  • Primitiva Menéndez

    (Servicio de Anatomía Patológica, Hospital Monte Naranco)

  • Xiao-Ou Shu

    (Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine)

  • Wei Lu

    (Shanghai Center for Disease Control and Prevention)

  • Yu-Tang Gao

    (Shanghai Cancer Institute)

  • Qiuyin Cai

    (Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine)

  • Angela Cox

    (CRUK/YCR Sheffield Cancer Research Centre, University of Sheffield)

  • Simon S. Cross

    (Academic Unit of Pathology)

  • Malcolm W. R. Reed

    (CRUK/YCR Sheffield Cancer Research Centre, University of Sheffield)

  • Irene L. Andrulis

    (Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
    University of Toronto)

  • Julia A. Knight

    (Dalla Lana School of Public Health University of Toronto
    Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital)

  • Gord Glendon

    (Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital)

  • Sandrine Tchatchou

    (Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital)

  • Elinor J. Sawyer

    (NIHR Comprehensive Biomedical Research Centre, Guy’s & St Thomas’ NHS Foundation Trust in partnership with King's College London)

  • Ian Tomlinson

    (Wellcome Trust Centre for Human Genetics, Oxford Biomedical Research Centre, University of Oxford)

  • Michael J. Kerin

    (Clinical Science Institute, University Hospital Galway)

  • Nicola Miller

    (Clinical Science Institute, University Hospital Galway)

  • Christopher A. Haiman

    (Keck School of Medicine University of Southern California Norris Comprehensive Cancer Center)

  • Brian E. Henderson

    (Keck School of Medicine University of Southern California Norris Comprehensive Cancer Center)

  • Fredrick Schumacher

    (Keck School of Medicine University of Southern California Norris Comprehensive Cancer Center)

  • Loic Le Marchand

    (Epidemiology Program, Cancer Research Center, University of Hawaii)

  • Annika Lindblom

    (Karolinska Institutet)

  • Sara Margolin

    (Karolinska Institutet)

  • Soo Hwang TEO

    (Breast Cancer Research Unit, University Malaya Cancer Research Institute, University Malaya Medical Centre
    Cancer Research Initiatives Foundation, Sime Darby Medical Centre)

  • Cheng Har YIP

    (Breast Cancer Research Unit, University Malaya Cancer Research Institute, University Malaya Medical Centre)

  • Daphne S. C. Lee

    (Cancer Research Initiatives Foundation, Sime Darby Medical Centre)

  • Tien Y. Wong

    (Singapore Eye Research Institute, National University of Singapore)

  • Maartje J. Hooning

    (Erasmus MC Cancer Institute)

  • John W. M. Martens

    (Erasmus MC Cancer Institute)

  • J. Margriet Collée

    (Erasmus University Medical Center)

  • Carolien H. M. van Deurzen

    (Erasmus University Medical Center)

  • John L. Hopper

    (Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, Melbourne School of Population Health, University of Melbourne)

  • Melissa C. Southey

    (The University of Melbourne)

  • Helen Tsimiklis

    (The University of Melbourne)

  • Miroslav K. Kapuscinski

    (Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, Melbourne School of Population Health, University of Melbourne)

  • Chen-Yang Shen

    (College of Public Health, China Medical University
    Institute of Biomedical Sciences, Academia Sinica)

  • Pei-Ei Wu

    (Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica)

  • Jyh-Cherng Yu

    (Tri-Service General Hospital)

  • Shou-Tung Chen

    (Changhua Christian Hospital)

  • Grethe Grenaker Alnæs

    (Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet)

  • Anne-Lise Borresen-Dale

    (Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet
    Institute of Clinical Medicine, University of Oslo (UiO))

  • Graham G. Giles

    (Cancer Epidemiology Centre, Cancer Council Victoria
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne)

  • Roger L. Milne

    (Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
    Cancer Epidemiology Centre, The Cancer Council Victoria)

  • Catriona McLean

    (Anatomical Pathology, The Alfred Hospital)

  • Kenneth Muir

    (Warwick Medical School, Warwick University
    Institute of Population Health, University of Manchester)

  • Artitaya Lophatananon

    (Warwick Medical School, Warwick University)

  • Sarah Stewart-Brown

    (Warwick Medical School, Warwick University)

  • Pornthep Siriwanarangsan

    (Ministry of Public Health)

  • Mikael Hartman

    (Yong Loo Lin School of Medicine National University of Singapore and National University Health System
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health System)

  • Hui Miao

    (Saw Swee Hock School of Public Health, National University of Singapore and National University Health System)

  • Shaik Ahmad Bin Syed Buhari

    (National University Health System)

  • Yik Ying Teo

    (Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
    National University of Singapore)

  • Peter A. Fasching

    (University of California at Los Angeles
    University Breast Center Franconia, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN)

  • Lothar Haeberle

    (University Breast Center Franconia, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN)

  • Arif B. Ekici

    (Institute of Human Genetics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg)

  • Matthias W. Beckmann

    (University Breast Center Franconia, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN)

  • Hermann Brenner

    (German Cancer Research Center (DKFZ)
    German Cancer Consortium (DKTK))

  • Aida Karina Dieffenbach

    (German Cancer Research Center (DKFZ)
    German Cancer Consortium (DKTK))

  • Volker Arndt

    (German Cancer Research Center (DKFZ))

  • Christa Stegmaier

    (Saarland Cancer Registry)

  • Anthony Swerdlow

    (Institute of Cancer Research
    Institute of Cancer Research)

  • Alan Ashworth

    (Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research)

  • Nick Orr

    (Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research)

  • Minouk J. Schoemaker

    (Institute of Cancer Research)

  • Montserrat García-Closas

    (Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research
    Institute of Cancer Research)

  • Jonine Figueroa

    (National Cancer Institute)

  • Stephen J. Chanock

    (National Cancer Institute)

  • Jolanta Lissowska

    (M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology)

  • Jacques Simard

    (Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center, Laval University)

  • Mark S. Goldberg

    (McGill University
    McGill University Health Centre, Royal Victoria Hospital)

  • France Labrèche

    (Université de Montréal)

  • Martine Dumont

    (Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center, Laval University)

  • Robert Winqvist

    (Laboratory of Cancer Genetics and Tumor Biology, NordLab Oulu/Oulu University Hospital University of Oulu)

  • Katri Pylkäs

    (Laboratory of Cancer Genetics and Tumor Biology, NordLab Oulu/Oulu University Hospital University of Oulu)

  • Arja Jukkola-Vuorinen

    (Oulu University Hospital, University of Oulu)

  • Hiltrud Brauch

    (Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology
    University of Tübingen
    German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ))

  • Thomas Brüning

    (Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA))

  • Yon-Dschun Koto

    (Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus)

  • Paolo Radice

    (Fondazione IRCCS Istituto Nazionale dei Tumori (INT))

  • Paolo Peterlongo

    (IFOM, Fondazione Istituto FIRC di Oncologia Molecolare)

  • Bernardo Bonanni

    (Istituto Europeo di Oncologia (IEO))

  • Sara Volorio

    (IFOM, Fondazione Istituto FIRC di Oncologia Molecolare
    Cogentech Cancer Genetic Test Laboratory)

  • Thilo Dörk

    (Hannover Medical School)

  • Natalia V. Bogdanova

    (Hannover Medical School)

  • Sonja Helbig

    (Hannover Medical School)

  • Arto Mannermaa

    (Cancer Center of Eastern Finland, University of Eastern Finland
    Imaging Center, Kuopio University Hospital
    School of Medicine, Institute of Clinical Medicine, Oncology, University of Eastern Finland)

  • Vesa Kataja

    (Cancer Center of Eastern Finland, University of Eastern Finland
    School of Medicine, Institute of Clinical Medicine, Oncology, University of Eastern Finland)

  • Veli-Matti Kosma

    (Cancer Center of Eastern Finland, University of Eastern Finland
    Imaging Center, Kuopio University Hospital
    School of Medicine, Institute of Clinical Medicine, Oncology, University of Eastern Finland)

  • Jaana M. Hartikainen

    (Cancer Center of Eastern Finland, University of Eastern Finland
    Imaging Center, Kuopio University Hospital
    School of Medicine, Institute of Clinical Medicine, Oncology, University of Eastern Finland)

  • Peter Devilee

    (Leiden University Medical Center)

  • Robert A. E. M. Tollenaar

    (Leiden University Medical Center)

  • Caroline Seynaeve

    (Family Cancer Clinic, Erasmus MC-Daniel den Hoed Cancer Centre)

  • Christi J. Van Asperen

    (Erasmus University Medical Center)

  • Anna Jakubowska

    (Pomeranian Medical University)

  • Jan Lubinski

    (Pomeranian Medical University)

  • Katarzyna Jaworska-Bieniek

    (Pomeranian Medical University)

  • Katarzyna Durda

    (Pomeranian Medical University)

  • Susan Slager

    (Mayo Clinic)

  • Amanda E. Toland

    (Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University)

  • Christine B. Ambrosone

    (Roswell Park Cancer Institute)

  • Drakoulis Yannoukakos

    (Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research ‘Demokritos’, Aghia Paraskevi Attikis)

  • Suleeporn Sangrajrang

    (National Cancer Institute)

  • Valerie Gaborieau

    (International Agency for Research on Cancer)

  • Paul Brennan

    (International Agency for Research on Cancer)

  • James McKay

    (International Agency for Research on Cancer)

  • Ute Hamann

    (Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ))

  • Diana Torres

    (Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ)
    Institute of Human Genetics, Pontificia University Javeriana)

  • Wei Zheng

    (Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine)

  • Jirong Long

    (Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine)

  • Hoda Anton-Culver

    (University of California Irvine)

  • Susan L. Neuhausen

    (Beckman Research Institute of City of Hope)

  • Craig Luccarini

    (Centre for Cancer Genetic Epidemiology)

  • Caroline Baynes

    (Centre for Cancer Genetic Epidemiology)

  • Shahana Ahmed

    (Centre for Cancer Genetic Epidemiology)

  • Mel Maranian

    (Centre for Cancer Genetic Epidemiology)

  • Catherine S. Healey

    (Centre for Cancer Genetic Epidemiology)

  • Anna González-Neira

    (Human Genotyping-CEGEN Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO))

  • Guillermo Pita

    (Human Genotyping-CEGEN Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO))

  • M. Rosario Alonso

    (Human Genotyping-CEGEN Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO))

  • Nuria Álvarez

    (Human Genotyping-CEGEN Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO))

  • Daniel Herrero

    (Human Genotyping-CEGEN Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO))

  • Daniel C. Tessier

    (Centre d’innovation Génome Québec et Université McGill)

  • Daniel Vincent

    (McGill University)

  • Francois Bacot

    (McGill University)

  • Ines de Santiago

    (Cancer Research UK, Cambridge Institute, University of Cambridge, Robinson Way)

  • Jason Carroll

    (Cancer Research UK, Cambridge Institute, University of Cambridge, Robinson Way)

  • Carlos Caldas

    (Cancer Research UK, Cambridge Institute, University of Cambridge, Robinson Way)

  • Melissa A. Brown

    (School of Chemistry and Molecular Biosciences, The University of Queensland)

  • Mathieu Lupien

    (The Princess Margaret Cancer Centre, University Health Network
    Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
    University of Toronto)

  • Vessela N. Kristensen

    (Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet
    Institute of Clinical Medicine, University of Oslo (UiO)
    University of Oslo (UiO))

  • Paul D P Pharoah

    (Centre for Cancer Genetic Epidemiology
    Centre for Cancer Genetic Epidemiology, University of Cambridge)

  • Georgia Chenevix-Trench

    (QIMR Berghofer Medical Research Institute)

  • Juliet D French

    (QIMR Berghofer Medical Research Institute
    School of Chemistry and Molecular Biosciences, The University of Queensland)

  • Douglas F. Easton

    (Centre for Cancer Genetic Epidemiology
    Centre for Cancer Genetic Epidemiology, University of Cambridge)

  • Alison M. Dunning

    (Centre for Cancer Genetic Epidemiology)

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.

Suggested Citation

  • 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 Be, 2014. "Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5999
    DOI: 10.1038/ncomms5999
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