. 2014 Nov 12;9(11):e109973.

doi: 10.1371/journal.pone.0109973. eCollection 2014.

MicroRNA related polymorphisms and breast cancer risk

Sofia Khan¹, Dario Greco², Kyriaki Michailidou³, Roger L Milne⁴, Taru A Muranen¹, Tuomas Heikkinen¹, Kirsimari Aaltonen⁵, Joe Dennis³, Manjeet K Bolla³, Jianjun Liu⁶, Per Hall⁷, Astrid Irwanto⁶, Keith Humphreys⁷, Jingmei Li⁶, Kamila Czene⁷, Jenny Chang-Claude⁸, Rebecca Hein⁹, Anja Rudolph⁸, Petra Seibold⁸, Dieter Flesch-Janys¹⁰, Olivia Fletcher¹¹, Julian Peto¹², Isabel dos Santos Silva¹², Nichola Johnson¹¹, Lorna Gibson¹², Zoe Aitken¹², John L Hopper¹³, Helen Tsimiklis¹⁴, Minh Bui¹³, Enes Makalic¹³, Daniel F Schmidt¹³, Melissa C Southey¹⁴, Carmel Apicella¹³, Jennifer Stone¹³, Quinten Waisfisz¹⁵, Hanne Meijers-Heijboer¹⁵, Muriel A Adank¹⁵, Rob B van der Luijt¹⁶, Alfons Meindl¹⁷, Rita K Schmutzler¹⁸, Bertram Müller-Myhsok¹⁹, Peter Lichtner²⁰, Clare Turnbull²¹, Nazneen Rahman²¹, Stephen J Chanock²², David J Hunter²³, Angela Cox²⁴, Simon S Cross²⁵, Malcolm W R Reed²⁴, Marjanka K Schmidt²⁶, Annegien Broeks²⁶, Laura J Van't Veer²⁶, Frans B Hogervorst²⁶, Peter A Fasching²⁷, Michael G Schrauder²⁸, Arif B Ekici²⁹, Matthias W Beckmann²⁸, Stig E Bojesen³⁰, Børge G Nordestgaard³⁰, Sune F Nielsen³⁰, Henrik Flyger³¹, Javier Benitez³², Pilar M Zamora³³, Jose I A Perez³⁴, Christopher A Haiman³⁵, Brian E Henderson³⁵, Fredrick Schumacher³⁵, Loic Le Marchand³⁶, Paul D P Pharoah³⁷, Alison M Dunning³⁸, Mitul Shah³⁸, Robert Luben³⁹, Judith Brown³, Fergus J Couch⁴⁰, Xianshu Wang⁴⁰, Celine Vachon⁴¹, Janet E Olson⁴¹, Diether Lambrechts⁴², Matthieu Moisse⁴², Robert Paridaens⁴³, Marie-Rose Christiaens⁴³, Pascal Guénel⁴⁴, Thérèse Truong⁴⁴, Pierre Laurent-Puig⁴⁵, Claire Mulot⁴⁵, Frederick Marme⁴⁶, Barbara Burwinkel⁴⁷, Andreas Schneeweiss⁴⁶, Christof Sohn⁴⁸, Elinor J Sawyer⁴⁹, Ian Tomlinson⁵⁰, Michael J Kerin⁵¹, Nicola Miller⁵¹, Irene L Andrulis⁵², Julia A Knight⁵³, Sandrine Tchatchou⁵⁴, Anna Marie Mulligan⁵⁵, Thilo Dörk⁵⁶, Natalia V Bogdanova⁵⁷, Natalia N Antonenkova⁵⁸, Hoda Anton-Culver⁵⁹, Hatef Darabi⁷, Mikael Eriksson⁷, Montserrat Garcia-Closas⁶⁰, Jonine Figueroa²², Jolanta Lissowska⁶¹, Louise Brinton²², Peter Devilee⁶², Robert A E M Tollenaar⁶³, Caroline Seynaeve⁶⁴, Christi J van Asperen⁶⁵, Vessela N Kristensen⁶⁶; kConFab Investigators; Australian Ovarian Cancer Study Group; Susan Slager⁴¹, Amanda E Toland⁶⁷, Christine B Ambrosone⁶⁸, Drakoulis Yannoukakos⁶⁹, Annika Lindblom⁷⁰, Sara Margolin⁷¹, Paolo Radice⁷², Paolo Peterlongo⁷³, Monica Barile⁷⁴, Paolo Mariani⁷⁵, Maartje J Hooning⁷⁶, John W M Martens⁷⁶, J Margriet Collée⁷⁷, Agnes Jager⁷⁶, Anna Jakubowska⁷⁸, Jan Lubinski⁷⁸, Katarzyna Jaworska-Bieniek⁷⁹, Katarzyna Durda⁷⁸, Graham G Giles⁴, Catriona McLean⁸⁰, Hiltrud Brauch⁸¹, Thomas Brüning⁸², Yon-Dschun Ko⁸³; GENICA Network; Hermann Brenner⁸⁴, Aida Karina Dieffenbach⁸⁴, Volker Arndt⁸⁵, Christa Stegmaier⁸⁶, Anthony Swerdlow⁸⁷, Alan Ashworth¹¹, Nick Orr¹¹, Michael Jones⁸⁸, Jacques Simard⁸⁹, Mark S Goldberg⁹⁰, France Labrèche⁹¹, Martine Dumont⁸⁹, Robert Winqvist⁹², Katri Pylkäs⁹², Arja Jukkola-Vuorinen⁹³, Mervi Grip⁹⁴, Vesa Kataja⁹⁵, Veli-Matti Kosma⁹⁶, Jaana M Hartikainen⁹⁶, Arto Mannermaa⁹⁶, Ute Hamann⁹⁷, Georgia Chenevix-Trench⁹⁸, Carl Blomqvist⁹⁹, Kristiina Aittomäki¹⁰⁰, Douglas F Easton³⁷, Heli Nevanlinna¹

Collaborators, Affiliations

Collaborators

Hiltrud Brauch, Wing-Yee Lo, Christina Justenhoven, Yon-Dschun Ko, Christian Baisch, Hans-Peter Fischer, Ute Hamann, Thomas Brüning, Beate Pesch, Sylvia Rabstein, Anne Lotz, Volker Harth, Morteza Aghmesheh, David Amor, Lesley Andrews, Yoland Antill, Shane Armitage, Leanne Arnold, Rosemary Balleine, Agnes Bankier, Patti Bastick, Jonathan Beesley, John Beilby, Barbara Bennett, Ian Bennett, Geoffrey Berry, Anneke Blackburn, Michael Bogwitz, Meagan Brennan, Melissa Brown, Michael Buckley, Matthew Burgess, Jo Burke, Phyllis Butow, Keith Byron, David Callen, Ian Campbell, Deepa Chauhan, Manisha Chauhan, Georgia Chenevix-Trench, Alice Christian, Christine Clarke, Alison Colley, Dick Cotton, Ashley Crook, James Cui, Bronwyn Culling, Margaret Cummings, Sarah-Jane Dawson, Anna deFazio, Martin Delatycki, Rebecca Dickson, Joanne Dixon, Alexander Dobrovic, Tracy Dudding, Ted Edkins, Stacey Edwards, Maurice Eisenbruch, Gelareh Farshid, Susan Fawcett, Andrew Fellows, Georgina Fenton, Michael Field, Frank Firgaira, James Flanagan, Jean Fleming, Peter Fong, John Forbes, Stephen Fox, Juliet French, Michael Friedlander, Clara Gaff, Mac Gardner, Mike Gattas, Peter George, Graham Giles, Grantley Gill, Jack Goldblatt, Sian Greening, Scott Grist, Eric Haan, Kate Hardie, Marion Harris, Stewart Hart, Nick Hayward, Sue Healey, Louise Heiniger, John Hopper, Evelyn Humphrey, Clare Hunt, Paul James, Mark Jenkins, Alison Jones, Rick Kefford, Alexa Kidd, Belinda Kiely, Judy Kirk, Jessica Koehler, James Kollias, Serguei Kovalenko, Sunil Lakhani, Amanda Leaming, Jennifer Leary, Jacqueline Lim, Geoff Lindeman, Lara Lipton, Liz Lobb, Graham Mann, Deborah Marsh, Sue Anne McLachlan, Bettina Meiser, Cliff Meldrum, Roger Milne, Gillian Mitchell, Beth Newman, Sophie Nightingale, Shona O'Connell, Imelda O'Loughlin, Richard Osborne, Nick Pachter, Briony Patterson, Lester Peters, Kelly Phillips, Melanie Price, Lynne Purser, Tony Reeve, Jeanne Reeve, Robert Richards, Edwina Rickard, Bridget Robinson, Barney Rudzki, Mona Saleh, Elizabeth Salisbury, Joe Sambrook, Christobel Saunders, Jodi Saunus, Robyn Sayer, Elizabeth Scott, Rodney Scott, Clare Scott, Ram Seshadri, Adrienne Sexton, Raghwa Sharma, Andrew Shelling, Peter Simpson, Melissa Southey, Amanda Spurdle, Graeme Suthers, Pamela Sykes, Donna Taylor, Jessica Taylor, Benjamin Thierry, Susan Thomas, Ella Thompson, Heather Thorne, Sharron Townshend, Alison Trainer, Lan Tran, Kathy Tucker, Janet Tyler, Jane Visvader, Logan Walker, Ian Walpole, Robin Ward, Paul Waring, Bev Warner, Graham Warren, Rachael Williams, Judy Wilson, Ingrid Winship, Kathy Wu, Mary Ann Young, R Stuart-Harris, F Kirsten, J Rutovitz, P Clingan, A Glasgow, A Proietto, S Braye, G Otton, J Shannon, T Bonaventura, J Stewart, S Begbie, M Friedlander, D Bell, S Baron-Hay, A Ferrier, G Gard, D Nevell, N Pavlakis, S Valmadre, B Young, C Camaris, R Crouch, L Edwards, N Hacker, D Marsden, G Robertson, P Beale, J Beith, J Carter, C Dalrymple, R Houghton, P Russell, L Anderson, M Links, J Grygiel, J Hill, A Brand, K Byth, R Jaworski, P Harnett, R Sharma, G Wain, D Purdie, D Whiteman, B Ward, D Papadimos, A Crandon, M Cummings, K Horwood, A Obermair, L Perrin, D Wyld, J Nicklin, M Davy, M K Oehler, C Hall, T Dodd, T Healy, K Pittman, D Henderson, J Miller, J Pierdes, A Achan, P Blomfield, D Challis, R McIntosh, A Parker, B Brown, R Rome, D Allen, P Grant, S Hyde, R Laurie, M Robbie, D Healy, T Jobling, T Manolitsas, J McNealage, P Rogers, B Susil, E Sumithran, I Simpson, I Haviv, K Phillips, D Rischin, S Fox, D Johnson, S Lade, P Waring, M Loughrey, N O'Callaghan, B Murray, L Mileshkin, P Allan, V Billson, J Pyman, D Neesham, M Quinn, A Hamilton, O McNally, C Underhill, R Bell, L F Ng, R Blum, V Ganju, I Hammond, A McCartney, C Stewart, Y Leung, M Buck, N Zeps

Affiliations

¹ Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
² Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Finnish Institute of Occupational Health, Helsinki, Finland.
³ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
⁴ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
⁵ Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Department of Clinical Genetics, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Department of Oncology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
⁶ Human Genetics Division, Genome Institute of Singapore, Singapore, Singapore.
⁷ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁸ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany.
¹⁰ Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom.
¹² Department of Non-Communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
¹³ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
¹⁴ Department of Pathology, The University of Melbourne, Melbourne, Australia.
¹⁵ Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
¹⁶ Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁷ Division of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany.
¹⁸ Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, Cologne, Germany; Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany; Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
¹⁹ Max Planck Institute of Psychiatry, Munich, Germany.
²⁰ Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
²¹ Section of Cancer Genetics, Institute of Cancer Research, Sutton, United Kingdom.
²² Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, United States of America.
²³ Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
²⁴ CRUK/YCR Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield, United Kingdom.
²⁵ Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom.
²⁶ Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands.
²⁷ University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Cancer Erlangen-EMN, Erlangen, Germany; David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California Los Angeles, California, United States of America.
²⁸ University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Cancer Erlangen-EMN, Erlangen, Germany.
²⁹ Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
³⁰ Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
³¹ Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
³² Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain.
³³ Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain.
³⁴ Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain.
³⁵ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
³⁶ Epidemiology Program, Cancer Research Center, University of Hawaii, Honolulu, Hawaii, United States of America.
³⁷ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
³⁸ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
³⁹ Clinical Gerontology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
⁴⁰ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.
⁴¹ Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
⁴² Vesalius Research Center (VRC), VIB, Leuven, Belgium; Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium.
⁴³ Oncology Department, University Hospital Gasthuisberg, Leuven, Belgium.
⁴⁴ Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, Villejuif, France; University Paris-Sud, UMRS 1018, Villejuif, France.
⁴⁵ Université Paris Sorbonne Cité, UMR-S775 Inserm, Paris, France.
⁴⁶ Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany; National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
⁴⁷ Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany; Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴⁸ Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
⁴⁹ Research Oncology, Division of Cancer Studies, King's College London, Guy's Hospital, London, United Kingdom.
⁵⁰ Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
⁵¹ Clinical Science Institute, University Hospital Galway, Galway, Ireland.
⁵² Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
⁵³ Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁵⁴ Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
⁵⁵ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine, and the Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
⁵⁶ Department of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
⁵⁷ Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
⁵⁸ N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
⁵⁹ Department of Epidemiology, University of California Irvine, Irvine, California, United States of America.
⁶⁰ Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, United Kingdom; Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research, London, United Kingdom.
⁶¹ Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
⁶² Department of Human Genetics & Department of Pathology, Leiden University Medical Center, Leiden, Netherlands.
⁶³ Department of Surgical Oncology, Leiden University Medical Center, Leiden, Netherlands.
⁶⁴ Family Cancer Clinic, Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, Netherlands.
⁶⁵ Department of Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands.
⁶⁶ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Clinical Molecular Biology (EpiGen), University of Oslo, Oslo, Norway; Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
⁶⁷ Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America.
⁶⁸ Roswell Park Cancer Institute, Buffalo, New York, United States of America.
⁶⁹ Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research "Demokritos", Aghia Paraskevi Attikis, Athens, Greece.
⁷⁰ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
⁷¹ Department of Oncology - Pathology, Karolinska Institutet, Stockholm, Sweden.
⁷² Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
⁷³ IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.
⁷⁴ Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy.
⁷⁵ IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy; Cogentech Cancer Genetic Test Laboratory, Milan, Italy.
⁷⁶ Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁷⁷ Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁷⁸ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
⁷⁹ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland; Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland.
⁸⁰ Anatomical Pathology, The Alfred Hospital, Melbourne, Australia.
⁸¹ Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany; University of Tübingen, Tübingen, Germany.
⁸² Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bochum, Germany.
⁸³ Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany.
⁸⁴ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
⁸⁵ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁸⁶ Saarland Cancer Registry, Saarbrücken, Germany.
⁸⁷ Division of Genetics and Epidemiology and Division of Breast Cancer Research, The Institute of Cancer Research, Sutton, Surrey, United Kingdom.
⁸⁸ Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, United Kingdom.
⁸⁹ Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec, Canada.
⁹⁰ Department of Medicine, McGill University, Montreal, Canada; Division of Clinical Epidemiology, McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec, Canada.
⁹¹ Départements de Santé Environnementale et Santé au Travail et de Médecine Sociale et Préventive, Université de Montréal, Montreal, Quebec, Canada.
⁹² Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, NordLab Oulu/Oulu University Hospital, Oulu, Finland.
⁹³ Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland.
⁹⁴ Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland.
⁹⁵ School of Medicine, Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland; Cancer Center, Kuopio University Hospital, Kuopio, Finland.
⁹⁶ School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland; Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland; Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland.
⁹⁷ Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁹⁸ Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
⁹⁹ Department of Oncology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
¹⁰⁰ Department of Clinical Genetics, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

PMID: 25390939
PMCID: PMC4229095
DOI: 10.1371/journal.pone.0109973

MicroRNA related polymorphisms and breast cancer risk

Sofia Khan et al. PLoS One. 2014.

. 2014 Nov 12;9(11):e109973.

doi: 10.1371/journal.pone.0109973. eCollection 2014.

Authors

Collaborators

Hiltrud Brauch, Wing-Yee Lo, Christina Justenhoven, Yon-Dschun Ko, Christian Baisch, Hans-Peter Fischer, Ute Hamann, Thomas Brüning, Beate Pesch, Sylvia Rabstein, Anne Lotz, Volker Harth, Morteza Aghmesheh, David Amor, Lesley Andrews, Yoland Antill, Shane Armitage, Leanne Arnold, Rosemary Balleine, Agnes Bankier, Patti Bastick, Jonathan Beesley, John Beilby, Barbara Bennett, Ian Bennett, Geoffrey Berry, Anneke Blackburn, Michael Bogwitz, Meagan Brennan, Melissa Brown, Michael Buckley, Matthew Burgess, Jo Burke, Phyllis Butow, Keith Byron, David Callen, Ian Campbell, Deepa Chauhan, Manisha Chauhan, Georgia Chenevix-Trench, Alice Christian, Christine Clarke, Alison Colley, Dick Cotton, Ashley Crook, James Cui, Bronwyn Culling, Margaret Cummings, Sarah-Jane Dawson, Anna deFazio, Martin Delatycki, Rebecca Dickson, Joanne Dixon, Alexander Dobrovic, Tracy Dudding, Ted Edkins, Stacey Edwards, Maurice Eisenbruch, Gelareh Farshid, Susan Fawcett, Andrew Fellows, Georgina Fenton, Michael Field, Frank Firgaira, James Flanagan, Jean Fleming, Peter Fong, John Forbes, Stephen Fox, Juliet French, Michael Friedlander, Clara Gaff, Mac Gardner, Mike Gattas, Peter George, Graham Giles, Grantley Gill, Jack Goldblatt, Sian Greening, Scott Grist, Eric Haan, Kate Hardie, Marion Harris, Stewart Hart, Nick Hayward, Sue Healey, Louise Heiniger, John Hopper, Evelyn Humphrey, Clare Hunt, Paul James, Mark Jenkins, Alison Jones, Rick Kefford, Alexa Kidd, Belinda Kiely, Judy Kirk, Jessica Koehler, James Kollias, Serguei Kovalenko, Sunil Lakhani, Amanda Leaming, Jennifer Leary, Jacqueline Lim, Geoff Lindeman, Lara Lipton, Liz Lobb, Graham Mann, Deborah Marsh, Sue Anne McLachlan, Bettina Meiser, Cliff Meldrum, Roger Milne, Gillian Mitchell, Beth Newman, Sophie Nightingale, Shona O'Connell, Imelda O'Loughlin, Richard Osborne, Nick Pachter, Briony Patterson, Lester Peters, Kelly Phillips, Melanie Price, Lynne Purser, Tony Reeve, Jeanne Reeve, Robert Richards, Edwina Rickard, Bridget Robinson, Barney Rudzki, Mona Saleh, Elizabeth Salisbury, Joe Sambrook, Christobel Saunders, Jodi Saunus, Robyn Sayer, Elizabeth Scott, Rodney Scott, Clare Scott, Ram Seshadri, Adrienne Sexton, Raghwa Sharma, Andrew Shelling, Peter Simpson, Melissa Southey, Amanda Spurdle, Graeme Suthers, Pamela Sykes, Donna Taylor, Jessica Taylor, Benjamin Thierry, Susan Thomas, Ella Thompson, Heather Thorne, Sharron Townshend, Alison Trainer, Lan Tran, Kathy Tucker, Janet Tyler, Jane Visvader, Logan Walker, Ian Walpole, Robin Ward, Paul Waring, Bev Warner, Graham Warren, Rachael Williams, Judy Wilson, Ingrid Winship, Kathy Wu, Mary Ann Young, R Stuart-Harris, F Kirsten, J Rutovitz, P Clingan, A Glasgow, A Proietto, S Braye, G Otton, J Shannon, T Bonaventura, J Stewart, S Begbie, M Friedlander, D Bell, S Baron-Hay, A Ferrier, G Gard, D Nevell, N Pavlakis, S Valmadre, B Young, C Camaris, R Crouch, L Edwards, N Hacker, D Marsden, G Robertson, P Beale, J Beith, J Carter, C Dalrymple, R Houghton, P Russell, L Anderson, M Links, J Grygiel, J Hill, A Brand, K Byth, R Jaworski, P Harnett, R Sharma, G Wain, D Purdie, D Whiteman, B Ward, D Papadimos, A Crandon, M Cummings, K Horwood, A Obermair, L Perrin, D Wyld, J Nicklin, M Davy, M K Oehler, C Hall, T Dodd, T Healy, K Pittman, D Henderson, J Miller, J Pierdes, A Achan, P Blomfield, D Challis, R McIntosh, A Parker, B Brown, R Rome, D Allen, P Grant, S Hyde, R Laurie, M Robbie, D Healy, T Jobling, T Manolitsas, J McNealage, P Rogers, B Susil, E Sumithran, I Simpson, I Haviv, K Phillips, D Rischin, S Fox, D Johnson, S Lade, P Waring, M Loughrey, N O'Callaghan, B Murray, L Mileshkin, P Allan, V Billson, J Pyman, D Neesham, M Quinn, A Hamilton, O McNally, C Underhill, R Bell, L F Ng, R Blum, V Ganju, I Hammond, A McCartney, C Stewart, Y Leung, M Buck, N Zeps

Affiliations

¹ Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
² Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Finnish Institute of Occupational Health, Helsinki, Finland.
³ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
⁴ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
⁵ Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Department of Clinical Genetics, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Department of Oncology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
⁶ Human Genetics Division, Genome Institute of Singapore, Singapore, Singapore.
⁷ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁸ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany.
¹⁰ Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom.
¹² Department of Non-Communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
¹³ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
¹⁴ Department of Pathology, The University of Melbourne, Melbourne, Australia.
¹⁵ Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
¹⁶ Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁷ Division of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany.
¹⁸ Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, Cologne, Germany; Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany; Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
¹⁹ Max Planck Institute of Psychiatry, Munich, Germany.
²⁰ Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
²¹ Section of Cancer Genetics, Institute of Cancer Research, Sutton, United Kingdom.
²² Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, United States of America.
²³ Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
²⁴ CRUK/YCR Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield, United Kingdom.
²⁵ Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom.
²⁶ Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands.
²⁷ University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Cancer Erlangen-EMN, Erlangen, Germany; David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California Los Angeles, California, United States of America.
²⁸ University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Cancer Erlangen-EMN, Erlangen, Germany.
²⁹ Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
³⁰ Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
³¹ Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
³² Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain.
³³ Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain.
³⁴ Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain.
³⁵ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
³⁶ Epidemiology Program, Cancer Research Center, University of Hawaii, Honolulu, Hawaii, United States of America.
³⁷ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
³⁸ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
³⁹ Clinical Gerontology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
⁴⁰ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.
⁴¹ Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
⁴² Vesalius Research Center (VRC), VIB, Leuven, Belgium; Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium.
⁴³ Oncology Department, University Hospital Gasthuisberg, Leuven, Belgium.
⁴⁴ Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, Villejuif, France; University Paris-Sud, UMRS 1018, Villejuif, France.
⁴⁵ Université Paris Sorbonne Cité, UMR-S775 Inserm, Paris, France.
⁴⁶ Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany; National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
⁴⁷ Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany; Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴⁸ Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
⁴⁹ Research Oncology, Division of Cancer Studies, King's College London, Guy's Hospital, London, United Kingdom.
⁵⁰ Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
⁵¹ Clinical Science Institute, University Hospital Galway, Galway, Ireland.
⁵² Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
⁵³ Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁵⁴ Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
⁵⁵ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine, and the Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
⁵⁶ Department of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
⁵⁷ Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
⁵⁸ N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
⁵⁹ Department of Epidemiology, University of California Irvine, Irvine, California, United States of America.
⁶⁰ Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, United Kingdom; Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research, London, United Kingdom.
⁶¹ Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
⁶² Department of Human Genetics & Department of Pathology, Leiden University Medical Center, Leiden, Netherlands.
⁶³ Department of Surgical Oncology, Leiden University Medical Center, Leiden, Netherlands.
⁶⁴ Family Cancer Clinic, Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, Netherlands.
⁶⁵ Department of Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands.
⁶⁶ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Clinical Molecular Biology (EpiGen), University of Oslo, Oslo, Norway; Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
⁶⁷ Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America.
⁶⁸ Roswell Park Cancer Institute, Buffalo, New York, United States of America.
⁶⁹ Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research "Demokritos", Aghia Paraskevi Attikis, Athens, Greece.
⁷⁰ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
⁷¹ Department of Oncology - Pathology, Karolinska Institutet, Stockholm, Sweden.
⁷² Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
⁷³ IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.
⁷⁴ Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy.
⁷⁵ IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy; Cogentech Cancer Genetic Test Laboratory, Milan, Italy.
⁷⁶ Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁷⁷ Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁷⁸ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
⁷⁹ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland; Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland.
⁸⁰ Anatomical Pathology, The Alfred Hospital, Melbourne, Australia.
⁸¹ Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany; University of Tübingen, Tübingen, Germany.
⁸² Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bochum, Germany.
⁸³ Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany.
⁸⁴ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
⁸⁵ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁸⁶ Saarland Cancer Registry, Saarbrücken, Germany.
⁸⁷ Division of Genetics and Epidemiology and Division of Breast Cancer Research, The Institute of Cancer Research, Sutton, Surrey, United Kingdom.
⁸⁸ Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, United Kingdom.
⁸⁹ Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec, Canada.
⁹⁰ Department of Medicine, McGill University, Montreal, Canada; Division of Clinical Epidemiology, McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec, Canada.
⁹¹ Départements de Santé Environnementale et Santé au Travail et de Médecine Sociale et Préventive, Université de Montréal, Montreal, Quebec, Canada.
⁹² Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, NordLab Oulu/Oulu University Hospital, Oulu, Finland.
⁹³ Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland.
⁹⁴ Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland.
⁹⁵ School of Medicine, Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland; Cancer Center, Kuopio University Hospital, Kuopio, Finland.
⁹⁶ School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland; Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland; Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland.
⁹⁷ Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁹⁸ Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
⁹⁹ Department of Oncology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
¹⁰⁰ Department of Clinical Genetics, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

PMID: 25390939
PMCID: PMC4229095
DOI: 10.1371/journal.pone.0109973

Abstract

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

**Figure 1. Workflow of miRNA SNP selection.**

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MicroRNA related polymorphisms and breast cancer risk

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MicroRNA related polymorphisms and breast cancer risk

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Conflict of interest statement

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