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Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

Authors :
Jirong Long
Simon S. Cross
Marc Tischkowitz
Beth Y. Karlan
Trinidad Caldés
Fergus J. Couch
Charlotte Sagne
Ute Hamann
Olga M. Sinilnikova
Maria Kabisch
Richard C Sallari
Gad Rennert
Daniel Barrowdale
Elinor J. Sawyer
Anthony J. Swerdlow
Jenny Lester
Åke Borg
Anders Bojesen
Rosa B. Barkardottir
Simon A. Gayther
Heli Nevanlinna
Judy Garber
Norbert Arnold
Vilde Drageset Haakensen
Vessela N. Kristensen
Christopher G. Scott
Daehee Kang
Gillian Mitchell
Eitan Friedman
Laura Ottini
Diether Lambrechts
Manjeet K. Bolla
Robert L. Nussbaum
Tomasz Huzarski
Dieter Niederacher
Angela Cox
Rachel Laframboise
Maartje J. Hooning
Volker Arndt
Penny Soucy
Marjanka K. Schmidt
William Blot
Soo Hwang Teo
Anne Lise Børresen-Dale
Maria A. Caligo
Ana Osorio
Orland Diez
Gertraud Maskarinec
Johanna Rantala
Kelly-Anne Phillips
Pascal Guénel
Hidemi Ito
Miquel Angel Pujana
Anna H. Wu
Christy G. Woolcott
Maya Ghoussaini
Hatef Darabi
Sander Canisius
Kay-Tee Khaw
Irene Konstantopoulou
Carl Blomqvist
Christine Rappaport
Joan Brunet
Hermann Brenner
Sylvie Mazoyer
Irene L. Andrulis
Nicholas A Sinnott-Armstrong
Javier Benitez
Claudine Isaacs
Mahdi Moradi Marjaneh
Joseph Vijai
Jennifer Stone
Qin Wang
Caroline Seynaeve
Patricia A. Ganz
Sara Margolin
Paolo Radice
Janet E. Olson
Soo-Chin Lee
Mark H. Greene
Laura Papi
Carmel Apicella
Ava Kwong
Mitul Shah
Matthias W. Beckmann
Yael Laitman
Hoda Anton-Culver
Ans M.W. van den Ouweland
Sue K. Park
Annegien Broeks
Georgia Chenevix-Trench
Jonathan Beesley
Nadja Bogdanova-Markov
Paolo Peterlongo
Paraskevi Apostolou
Bernardo Bonanni
Frederik Marmé
Veli-Matti Kosma
Alfons Meindl
Brian E. Henderson
Rulla M. Tamimi
Siranoush Manoukian
Bent Ejlertsen
Miroslav Kapuscinski
Juliet D. French
Mark E. Sherman
Ji Yeob Choi
Graham G. Giles
Stacey L. Edwards
Evgeny N. Imyanitov
Kamila Czene
Thomas Hansen
Nick Orr
Susanne Kaufmann
Lenka Foretova
Celine M. Vachon
Edith Olah
Anja Rudolph
Arto Mannermaa
Phuong L. Mai
Isabel dos-Santos-Silva
Haran Sivakumaran
Francesca Damiola
Christian F. Singer
Muhammad Usman Rashid
Ed Dicks
Mikael Hartman
Antonis C. Antoniou
Dominique Stoppa-Lyonnet
Douglas F. Easton
Alison M. Dunning
John L. Hopper
Nadine Tung
Annika Lindblom
Kristiina Aittomäki
Kenneth Muir
Sue Healey
Cheng Har Yip
Mads Thomassen
Melissa C. Southey
Ramunas Janavicius
Cecilia M. Dorfling
Christine B. Ambrosone
Siddhartha Kar
Mary B. Daly
Artitaya Lophatananon
Rachel Rando
Banu Arun
Christopher A. Haiman
Catherine M. Phelan
Margaret Hills
Manuel R. Teixeira
Diana Torres
Hans Wildiers
Andrew K. Godwin
Keith Humphreys
Katri Pylkäs
Monika Jarosz
Susan L. Neuhausen
Montserrat Garcia-Closas
Robert Winqvist
Joe Dennis
Sook-Yee Yoon
Wei Zheng
Mitch Dowsett
Gord Glendon
Natasha Bogdanova
Suleeporn Sangrajrang
Steve Ellis
Paul Brennan
Lee Eunjung
Keitaro Matsuo
Jacek Gronwald
David E. Goldgar
Debra Frost
Chiu-Chen Tseng
Henrik Flyger
Kristine M. Hillman
Susan M. Domchek
Elena Lopez-Knowles
Bernard Peissel
Anna von Wachenfeldt
Karoline Kuchenbaecker
Anna Jakubowska
Paul D.P. Pharoah
Jose Ignacio Arias Perez
Kim De Leeneer
Roger L. Milne
Peter A. Fasching
Louise Izatt
Saundra S. Buys
Lesley McGuffog
Elizabeth J. van Rensburg
Pei-Ei Wu
Peter Devilee
Åslaug Helland
Qiuyin Cai
Peter J. Hulick
Miguel de la Hoya
Esther M. John
Kerstin Rhiem
Jan Lubinski
Karen A. Pooley
Marion Piedmonte
Catherine S. Healey
Mark S. Goldberg
Xiao-Ou Shu
Antoinette Hollestelle
Mary Beth Terry
Jenny Chang-Claude
Silje Nord
Chen-Yang Shen
Hiltrud Brauch
Kathleen Claes
Jason Sang Hun Lee
Sofia Khan
Katherine L. Nathanson
Hans Ehrencrona
Olufunmilayo I. Olopade
Stig E. Bojesen
Matti A. Rookus
Andrew Lee
Rita K. Schmutzler
Julian Peto
Jeffrey N. Weitzel
Barbara Burwinkel
Arjen R. Mensenkamp
Jacques Simard
Yu-Tang Gao
Robert Luben
S. Drury
Thilo Dörk
Laima Tihomirova
Per Hall
Barbara Perkins
Simona Agata
Jonine D. Figueroa
Julia A. Knight
Kenneth Offit
Kyriaki Michailidou
Anna González-Neira
Ian Tomlinson
Thérèse Truong
Amanda E. Toland
Anna Marie Mulligan
Noralane M. Lindor
Deborah J. Thompson
Marco Montagna
Clinical Genetics
Medical Oncology
Obstetrics & Gynecology
Dunning, Alison [0000-0001-6651-7166]
Thompson, Deborah [0000-0003-1465-5799]
Pooley, Karen [0000-0002-1274-9460]
Dicks, Ed [0000-0002-0617-0401]
Dennis, Joe [0000-0003-4591-1214]
Wang, Jean [0000-0002-9139-0627]
Ghoussaini, Maya [0000-0002-2415-2143]
Lee, Andrew [0000-0003-0677-0252]
Tischkowitz, Marc [0000-0002-7880-0628]
Luben, Robert [0000-0002-5088-6343]
Khaw, Kay-Tee [0000-0002-8802-2903]
Pharoah, Paul [0000-0001-8494-732X]
Antoniou, Antonis [0000-0001-9223-3116]
Easton, Douglas [0000-0003-2444-3247]
Apollo - University of Cambridge Repository
Targeted Gynaecologic Oncology (TARGON)
Damage and Repair in Cancer Development and Cancer Treatment (DARE)
[ 1 ] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England [ 2 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England [ 3 ] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld, Australia [ 4 ] Breakthrough Breast Canc Res Ctr, Breast Canc Res, London, England [ 5 ] Royal Marsden Hosp, Acad Biochem, London SW3 6JJ, England [ 6 ] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA [ 7 ] MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA [ 8 ] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands [ 9 ] Univ Melbourne, Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia [ 10 ] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia [ 11 ] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England [ 12 ] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England [ 13 ] Univ Erlangen Nurnberg, Univ Hosp Erlangen, 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Source :
Nature Genetics, 48(4), 374-386. Nature Publishing Group, Nature Genetics, 48(4), 374, Dunning, A M, Michailidou, K, Kuchenbaecker, K B, Thompson, D J, French, J D, Beesley, J, Healey, C S, Kar, S, Pooley, K A, Lopez-Knowles, E, Dicks, E, Barrowdale, D, Sinnott-Armstrong, N A, Sallari, R C, Hillman, K M, Kaufmann, S, Sivakumaran, H, Moradi Marjaneh, M, Lee, J S, Hills, M, Jarosz, M, Drury, S, Canisius, S, Bolla, M K, Dennis, J, Wang, Q, Hopper, J L, Southey, M C, Broeks, A, Schmidt, M K, Lophatananon, A, Muir, K, Beckmann, M W, Fasching, P A, Dos Santos Silva, I, Peto, J, Sawyer, E J, Tomlinson, I, Burwinkel, B, Marme, F, Guénel, P, Truong, T, Bojesen, S E, Flyger, H, González-Neira, A, Perez, J I A, Shen, C-Y, Hansen, T V O, Bojesen, A, Thomassen, M & EMBRACE 2016, ' Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170 ', Nature Genetics, vol. 48, no. 4, pp. 374-386 . https://doi.org/10.1038/ng.3521, Nature Genetics, 48(4), 374-+. Nature Publishing Group, Recercat. Dipósit de la Recerca de Catalunya, instname, Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, Dipòsit Digital de la UB, Universidad de Barcelona, Dunning, A M, Michailidou, K, Kuchenbaecker, K B, Thompson, D, French, J D, Beesley, J, Healey, C S, Kar, S, Pooley, K A, Lopez-Knowles, E, Dicks, E, Barrowdale, D, Sinnott-Armstrong, N A, Sallari, R C, Hillman, K M, Kaufmann, S, Sivakumaran, H, Moradi Marjaneh, M, Lee, J S, Hills, M, Jarosz, M, Drury, S, Canisius, S, Bolla, M K, Dennis, J, Wang, Q, Hopper, J L, Southey, M C, Broeks, A, Schmidt, M K, Lophatananon, A, Muir, K, Beckmann, M W, Fasching, P A, Dos-Santos-Silva, I, Peto, J, Sawyer, E J, Tomlinson, I, Burwinkel, B, Marme, F, Guénel, P, Truong, T, Bojesen, S E, Flyger, H, González-Neira, A & Perez, J I A & Anton-Culver, H & Eunjung, L & Arndt, V & Figueroa, J 2016, ' Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170 ', Nature Genetics, vol. 48, no. 4, pp. 374-386 . https://doi.org/10.1038/ng.3521, Nature Genetics, 48, 374-86, Nature Genetics, 48, 4, pp. 374-86
Publication Year :
2016

Abstract

To access publisher's full text version of this article click on the hyperlink at the bottom of the page We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression. National Institute for Health Research (NIHR) info:eu-repo/grantAgreement/EC/FP7/223175 Cancer Research UK C1287/A10118 C1287/A10710 C12292/A11174 C1281/A12014 C5047/A8384 C5047/A15007 C5047/A10692 C8197/A16565 US National Institutes of Health (NIH) CA128978 CA192393 CA116167 CA176785 US National Institutes of Health (NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer) CA116201 Post-Cancer GWAS initiative 1U19 CA148537 1U19 CA148065 1U19 CA148112 Post-Cancer GWAS initiative (GAME-ON initiative) US Department of Defense W81XWH-10-1-0341 Canadian Institutes of Health Research (CIHR) Komen Foundation for the Cure Breast Cancer Research Foundation Ovarian Cancer Research Fund

Details

Language :
English
ISSN :
10614036
Database :
OpenAIRE
Journal :
Nature Genetics, 48(4), 374-386. Nature Publishing Group, Nature Genetics, 48(4), 374, Dunning, A M, Michailidou, K, Kuchenbaecker, K B, Thompson, D J, French, J D, Beesley, J, Healey, C S, Kar, S, Pooley, K A, Lopez-Knowles, E, Dicks, E, Barrowdale, D, Sinnott-Armstrong, N A, Sallari, R C, Hillman, K M, Kaufmann, S, Sivakumaran, H, Moradi Marjaneh, M, Lee, J S, Hills, M, Jarosz, M, Drury, S, Canisius, S, Bolla, M K, Dennis, J, Wang, Q, Hopper, J L, Southey, M C, Broeks, A, Schmidt, M K, Lophatananon, A, Muir, K, Beckmann, M W, Fasching, P A, Dos Santos Silva, I, Peto, J, Sawyer, E J, Tomlinson, I, Burwinkel, B, Marme, F, Guénel, P, Truong, T, Bojesen, S E, Flyger, H, González-Neira, A, Perez, J I A, Shen, C-Y, Hansen, T V O, Bojesen, A, Thomassen, M & EMBRACE 2016, ' Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170 ', Nature Genetics, vol. 48, no. 4, pp. 374-386 . https://doi.org/10.1038/ng.3521, Nature Genetics, 48(4), 374-+. Nature Publishing Group, Recercat. Dipósit de la Recerca de Catalunya, instname, Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, Dipòsit Digital de la UB, Universidad de Barcelona, Dunning, A M, Michailidou, K, Kuchenbaecker, K B, Thompson, D, French, J D, Beesley, J, Healey, C S, Kar, S, Pooley, K A, Lopez-Knowles, E, Dicks, E, Barrowdale, D, Sinnott-Armstrong, N A, Sallari, R C, Hillman, K M, Kaufmann, S, Sivakumaran, H, Moradi Marjaneh, M, Lee, J S, Hills, M, Jarosz, M, Drury, S, Canisius, S, Bolla, M K, Dennis, J, Wang, Q, Hopper, J L, Southey, M C, Broeks, A, Schmidt, M K, Lophatananon, A, Muir, K, Beckmann, M W, Fasching, P A, Dos-Santos-Silva, I, Peto, J, Sawyer, E J, Tomlinson, I, Burwinkel, B, Marme, F, Guénel, P, Truong, T, Bojesen, S E, Flyger, H, González-Neira, A & Perez, J I A & Anton-Culver, H & Eunjung, L & Arndt, V & Figueroa, J 2016, ' Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170 ', Nature Genetics, vol. 48, no. 4, pp. 374-386 . https://doi.org/10.1038/ng.3521, Nature Genetics, 48, 374-86, Nature Genetics, 48, 4, pp. 374-86
Accession number :
edsair.doi.dedup.....9243da2133c0ff63e63cff70cb87aac9
Full Text :
https://doi.org/10.1038/ng.3521