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

dc.contributor.authorDunning, Alison M.
dc.contributor.authorMichailidou, Kyriaki
dc.contributor.authorKuchenbaecker, Karoline B.
dc.contributor.authorThompson, Deborah
dc.contributor.authorFrench, Juliet D.
dc.contributor.authorBeesley, Jonathan
dc.contributor.authorHealey, Catherine S.
dc.contributor.authorKar, Siddhartha
dc.contributor.authorPooley, Karen A.
dc.contributor.authorLopez-Knowles, Elena
dc.contributor.authorDicks, Ed
dc.contributor.authorBarrowdale, Daniel
dc.contributor.authorSinnott-Armstrong, Nicholas A.
dc.contributor.authorSallari, Richard C.
dc.contributor.authorHillman, Kristine M.
dc.contributor.authorKaufmann, Susanne
dc.contributor.authorSivakumaran, Haran
dc.contributor.authorMarjaneh, Mahdi Moradi
dc.contributor.authorLee, Jason S.
dc.contributor.authorHills, Margaret
dc.contributor.authorJarosz, Monika
dc.contributor.authorDrury, Suzie
dc.contributor.authorCanisius, Sander
dc.contributor.authorBolla, Manjeet K.
dc.contributor.authorDennis, Joe
dc.contributor.authorWang, Qin
dc.contributor.authorHopper, John L.
dc.contributor.authorSouthey, Melissa C.
dc.contributor.authorBroeks, Annegien
dc.contributor.authorSchmidt, Marjanka K.
dc.contributor.authorLophatananon, Artitaya
dc.contributor.authorMuir, Kenneth
dc.contributor.authorBeckmann, Matthias W.
dc.contributor.authorFasching, Peter A.
dc.contributor.authorDos-Santos-Silva, Isabel
dc.contributor.authorPeto, Julian
dc.contributor.authorSawyer, Elinor J.
dc.contributor.authorTomlinson, Ian
dc.contributor.authorBurwinkel, Barbara
dc.contributor.authorMarme, Frederik
dc.contributor.authorGuenel, Pascal
dc.contributor.authorTruong, Therese
dc.contributor.authorBojesen, Stig E.
dc.contributor.authorFlyger, Henrik
dc.contributor.authorGonzalez-Neira, Anna
dc.contributor.authorPerez, Jose I.A.
dc.contributor.authorAnton-Culver, Hoda
dc.contributor.authorEunjung, Lee
dc.contributor.authorArndt, Volker
dc.contributor.authorBrenner, Hermann
dc.contributor.authorMeindl, Alfons
dc.contributor.authorSchmutzler, Rita K.
dc.contributor.authorBrauch, Hamann
dc.contributor.authorUte Hiltrud
dc.contributor.authorAittomaki, Kristiina
dc.contributor.authorBlomqvist, Carl
dc.contributor.authorIto, Hidemi
dc.contributor.authorMatsuo, Keitaro
dc.contributor.authorBogdanova, Natasha
dc.contributor.authorDork, Thilo
dc.contributor.authorLindblom, Margolin
dc.contributor.authorSara Annika
dc.contributor.authorKosma, Veli-Matti
dc.contributor.authorMannermaa, Arto
dc.contributor.authorTseng, Chiu-chen
dc.contributor.authorWu, Anna H.
dc.contributor.authorLambrechts, Diether
dc.contributor.authorWildiers, Hans
dc.contributor.authorChang-Claude, Jenny
dc.contributor.authorRudolph, Anja
dc.contributor.authorPeterlongo, Paolo
dc.contributor.authorRadice, Paolo
dc.contributor.authorOlson, Janet E.
dc.contributor.authorGiles, Graham G.
dc.contributor.authorMilne, Roger L.
dc.contributor.authorHaiman, Christopher A.
dc.contributor.authorHenderson, Brian E.
dc.contributor.authorGoldberg, Mark S.
dc.contributor.authorTeo, Soo H.
dc.contributor.authorYip, Cheng Har
dc.contributor.authorSilje, Nord
dc.contributor.authorBorresen-Dale, Anne-Lise
dc.contributor.authorKristensen, Vessela
dc.contributor.authorLong, Jirong
dc.contributor.authorZheng, Wei
dc.contributor.authorPylkas, Katri
dc.contributor.authorWinqvist, Robert
dc.contributor.authorAndrulis, Irene L.
dc.contributor.authorDevilee, Peter
dc.contributor.authorSeynaeve, Caroline
dc.contributor.authorFigueroa, Jonine
dc.contributor.authorSherman, Mark E.
dc.contributor.authorCzene, Kamila
dc.contributor.authorDarabi, Hatef
dc.contributor.authorHollestelle, Antoinette
dc.contributor.authorVan den Ouweland, Ans M.W.
dc.contributor.authorHumphreys, Keith
dc.contributor.authorGao, Yu-Tang
dc.contributor.authorShu, Xiao-Ou
dc.contributor.authorCox, Angela
dc.contributor.authorCross, Simon S.
dc.contributor.authorBlot, William
dc.contributor.authorCai, Qiuyin
dc.contributor.authorGhoussaini, Maya
dc.contributor.authorPerkins, Babara J.
dc.contributor.authorShah, Mitul
dc.contributor.authorChoi, Ji-Yeob
dc.contributor.authorKang, Daehee
dc.contributor.authorLee, Soo Chin
dc.contributor.authorHartman, Mikael
dc.contributor.authorKabisch, Maria
dc.contributor.authorTorres, Diana
dc.contributor.authorJakubowska, Anna
dc.contributor.authorLubinski, Jan
dc.contributor.authorBrennan, Paul
dc.contributor.authorSangrajrang, Suleeporn
dc.contributor.authorAmbrosone, Christine B.
dc.contributor.authorToland, Amanda Ewart
dc.contributor.authorShen, Chen-Yang
dc.contributor.authorWu, Pei-Ei
dc.contributor.authorOrr, Nick
dc.contributor.authorSwerdlow, Anthony
dc.contributor.authorMcGuffog, Lesley
dc.contributor.authorHealey, Sue
dc.contributor.authorLee, Andrew
dc.contributor.authorKapuscinski, Miroslav
dc.contributor.authorJohn, Esther M.
dc.contributor.authorTerry, Mary Beth
dc.contributor.authorDaly, Mary B.
dc.contributor.authorGoldgar, David E.
dc.contributor.authorBuys, Saundra S.
dc.contributor.authorJanavicius, Ramunas
dc.contributor.authorTihomirova, Laima
dc.contributor.authorTung, Nadine
dc.contributor.authorDorfling, Cecilia Maria
dc.contributor.authorJanse van Rensburg, E.S. (Elsie)
dc.contributor.authorNeuhausen, Susan L.
dc.contributor.authorEjlertsen, Bent
dc.contributor.authorHansen, Thomas V.O.
dc.contributor.authorOsorio, Ana
dc.contributor.authorBenitez, Javier
dc.contributor.authorRando, Rachel
dc.contributor.authorWeitzel, Jeffrey N.
dc.contributor.authorBonanni, Bernardo
dc.contributor.authorPeissel, Bernard
dc.contributor.authorManoukian, Siranoush
dc.contributor.authorPapi, Laura
dc.contributor.authorOttini, Laura
dc.contributor.authorKonstantopoulou, Irene
dc.contributor.authorApostolou, Paraskevi
dc.contributor.authorGarber, Judy
dc.contributor.authorFrost, Debra
dc.contributor.authorRashid, Muhammad Usman
dc.contributor.authorEMBRACE
dc.contributor.authorIzatt, Louise
dc.contributor.authorEllis, Steve
dc.contributor.authorGodwin, Andrew K.
dc.contributor.authorArnold, Norbert
dc.contributor.authorNiederacher, Dieter
dc.contributor.authorRhiem, Kerstin
dc.contributor.authorBogdanova-Markov, Nadja
dc.contributor.authorSagne, Charlotte
dc.contributor.authorStoppa-Lyonnet, Dominique
dc.contributor.authorDamiola, Francesca
dc.contributor.authorGEMO Study Collaborators
dc.contributor.authorSinilnikova, Olga M.
dc.contributor.authorMazoyer, Sylvie
dc.contributor.authorIsaacs, Claudine
dc.contributor.authorClaes, Kathleen B.M.
dc.contributor.authorDe Leeneer, Kim
dc.contributor.authorDe la Hoya, Miguel
dc.contributor.authorCaldes, Trinidad
dc.contributor.authorNevanlinna, Heli
dc.contributor.authorKhan, Sofia
dc.contributor.authorMensenkamp, Arjen R.
dc.contributor.authorHEBON
dc.contributor.authorHooning, Maartje J.
dc.contributor.authorRookus, Matti A.
dc.contributor.authorKwong, Ava
dc.contributor.authorOlah, Edith
dc.contributor.authorDiez, Orland
dc.contributor.authorBrunet, Joan
dc.contributor.authorPujana, Miquel Angel
dc.contributor.authorGronwald, Jacek
dc.contributor.authorHuzarski, Tomasz
dc.contributor.authorBarkardottir, Rosa B.
dc.contributor.authorLaframboise, Rachel
dc.contributor.authorSoucy, Penny
dc.contributor.authorMontagna, Marco
dc.contributor.authorAgata, Simona
dc.contributor.authorTeixeira, Manuel R.
dc.contributor.authorkConFab Investigators
dc.contributor.authorPark, Sue Kyung
dc.contributor.authorLindor, Noralane
dc.contributor.authorCouch, Fergus J.
dc.contributor.authorTischkowitz, Marc
dc.contributor.authorForetova, Lenka
dc.contributor.authorVijai, Joseph
dc.contributor.authorOffit, Kenneth
dc.contributor.authorSinger, Christian F.
dc.contributor.authorRappaport, Christine
dc.contributor.authorPhelan, Catherine M.
dc.contributor.authorGreene, Mark H.
dc.contributor.authorMai, Phuong L.
dc.contributor.authorRennert, Gad
dc.contributor.authorImyanitov, Evgeny N.
dc.contributor.authorHulick, Peter J.
dc.contributor.authorPhillips, Kelly-Anne
dc.contributor.authorPiedmonte, Marion
dc.contributor.authorMulligan, Anna Marie
dc.contributor.authorGlendon, Gord
dc.contributor.authorBojesen, Anders
dc.contributor.authorThomassen, Mads
dc.contributor.authorCaligo, Maria A.
dc.contributor.authorYoon, Sook-Yee
dc.contributor.authorFriedman, Eitan
dc.contributor.authorLaitman, Yael
dc.contributor.authorBorg, Ake
dc.contributor.authorVon Wachenfeldt, Anna
dc.contributor.authorEhrencrona, Hans
dc.contributor.authorRantala, Johanna
dc.contributor.authorOlopade, Olufunmilayo I.
dc.contributor.authorGanz, Patricia A.
dc.contributor.authorNussbaum, Robert L.
dc.contributor.authorGayther, Simon A.
dc.contributor.authorNathanson, Katherine L.
dc.contributor.authorDomchek, Susan M.
dc.contributor.authorArun, Banu K.
dc.contributor.authorMitchell, Gillian
dc.contributor.authorKarlan, Beth Y.
dc.contributor.authorLester, Jenny
dc.contributor.authorMaskarinec, Gertraud
dc.contributor.authorWoolcott, Christy
dc.contributor.authorScott, Christopher
dc.contributor.authorHaakensen, Vilde
dc.contributor.authorDowsett, Mitch
dc.contributor.authorPharoah, Paul D.P.
dc.contributor.authorSimard, Jacques
dc.contributor.authorHall, Per
dc.contributor.authorGarcía-Closas, Montserrat
dc.contributor.authorVachon, Celine
dc.contributor.authorChenevix-Trench, Georgia
dc.contributor.authorAntoniou, Antonis C.
dc.contributor.authorEaston, Douglas F.
dc.contributor.authorEdwards, Stacey L.
dc.date.accessioned2016-08-01T05:16:58Z
dc.date.issued2016-04
dc.description.abstractWe analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor a) 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.en_ZA
dc.description.departmentGeneticsen_ZA
dc.description.embargo2016-10-31
dc.description.librarianam2016en_ZA
dc.description.sponsorshipFunding for the iCOGS infrastructure came from the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692 and C8197/A16565), the US National Institutes of Health (NIH; CA128978, CA192393, CA116167, CA176785 and an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201)) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112, the GAME-ON initiative), the US Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Komen Foundation for the Cure, the Breast Cancer Research Foundation and the Ovarian Cancer Research Fund.en_ZA
dc.description.urihttp://www.nature.com/ngen_ZA
dc.identifier.citationDunning, AM, Michailidou, K, Kuchenbaecker, KB, Thompson, D, French, JD, Beesley, J, Healey, CS, Kar, S, Pooley, KA, Lopez-Knowles, E, Dicks, E, Barrowdale, D, Sinnott-Armstrong, NA, Sallari, RC, Hillman, KM, Kaufmann, S, Sivakumaran, H, Marjaneh, MM, Lee, JS, Hills, M, Jarosz, M, Drury, S, Canisius, S, Bolla, MK, Dennis, J, Wang, Q, Hopper, JL, Southey, MC, Broeks, A, Schmidt, MK, Lophatananon, A, Muir, K,Beckmann, MW, Fasching, PA,Ddos-Santos-Silva, I, Peto, J, Sawyer, EJ, Tomlinson, I, Burwinkel, B, Marme, F, Guenel, P, Truong, T, EBojesen, S, Flyger, H, González-Neira, A, Perez, JIA, Anton-Culver, H, Eunjung, L, Arndt, V, Hermann BrennerH, Meindl, A, Schmutzler, RK, Brauch, H, Hamann, U, Aittomaki, K, Blomqvist, C, Ito, H, Matsuo, K, Bogdanova, N, Dork, T, Lindblom, A, Margolin, S, Kosma, V-M, Mannermaa, A, Tseng, C-C, Wu, AH, Lambrechts, D, Wildiers, H, Chang-Claude, J, Rudolph, A, Peterlongo, P, Radice, P, Olson, JE, Giles, GG, Milne, RL, Haiman, CA, Henderson, BE, Goldberg, MS, Teo, SH, Yip, CH, Nord, S, Borresen-Dale, A-L, Kristensen, V, Long, J, Zheng, W, Pylkas, K, Winqvist, R, Andrulis, IL, Knight, JA, Devilee, P, Seynaeve, C, Figueroa, J, ESherman, M, Czene, K, Darabi, H, Hollestelle, A, van den Ouweland, AMW, Humphreys, K, Gao, Y-T, Shu, X-O, Cox, A, Cross, SS, Blot, W, Cai, Q, Ghoussaini, M, Perkins, BJ, Shah, M, Choi, J-Y, Kang, D, Lee, SC, Hartman, M, Kabisch, M, Torres, D, Jakubowska, A, Lubinski, J, Brennan, P, Sangrajrang, S, Ambrosone, CB, Toland, AE, Shen, C-Y, Wu, P-E, Orr, N, Swerdlow, A, McGuffog, L, Healey, S, Lee, A, Kapuscinski, M, John, EM, Terry, MB, Daly, MB, Goldgar, DE, Buys, SS, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, CM, Van Rensburg, EJ, Neuhausen, SL, Ejlertsen, B, Hansen, TVO, Osorio, A, Benitez, J, Rando, R, Weitzel, JN, Bonanni, B, Peissel, B, Manoukian, S, Papi, L, Ottini, L, Konstantopoulou, I, Apostolou, P, Garber, J, Rashid, MU, Frost, D, EMBRACE, Izatt, L, Ellis, S, Godwin, AK, Arnold, N, Niederacher, D, Rhiem, K, Bogdanova-Markov, N, Sagne, C, Stoppa-Lyonnet, D, Damiola, F, GEMO Study Collaborators, Sinilnikova, OM, Mazoyer, S, Isaacs, C, Claes, KBM, De Leeneer, K, De la Hoya, M, Caldes, T, Nevanlinna, H, Khan, S, Mensenkamp, AR, HEBON, Hooning, MJ, Rookus, MA, Kwong, A, Olah, E, Diez, O, Brunet, J, Pujana, MA, Gronwald, J, Huzarski, T, Barkardottir, RB, Laframboise, R, Soucy, P, Montagna, M, Agata, S, Teixeira, MR, kConFab Investigators, Park, SK, Lindor, N, Couch, FJ, Tischkowitz, M, Foretova, L, Vijai, J, Offit, K, Singer, CF, Rappaport, C, Phelan, CM, Greene, MH, Mai, PL, Rennert, G, NImyanitov, E, Hulick, PJ, Phillips, K-A, Piedmonte, M, Mulligan, AM, Glendon, G, Bojesen, A, Thomassen, M, Caligo, MA, Yoon, S-Y, Friedman, E, Laitman, Y, Borg, A, Von Wachenfeldt, A, Ehrencrona, H, Rantala, J, Olopade, OI, Ganz, PA, Nussbaum, RL, Gayther, SA, Nathanson, KL, Domchek, SM, Karun, B, Mitchell, G, Karlan, BY, Lester, J, Maskarinec, G, Woolcott, C, Scott, C, Stone, J, Apicella, C, Tamimi, R, Luben, R, Khaw, K-T, Helland, A, Haakensen, V, Dowsett, M, Pharoah, PDP, Simard, J, Hall, P, García-Closas, M, Vachon, C, Chenevix-Trench, G, Antoniou, AC, Easton, DF & Edwards, SL 2016, ‘Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170', Nature Genetics, vol. 48, no. 4, pp. 374-388.en_ZA
dc.identifier.issn1061-4036 (print)
dc.identifier.issn1546-1718 (online)
dc.identifier.other10.1038/ng.3521
dc.identifier.urihttp://hdl.handle.net/2263/56135
dc.language.isoenen_ZA
dc.publisherNature Publishing Groupen_ZA
dc.rights© 2016 Nature America, Inc. All rights reserved.en_ZA
dc.subjectVariantsen_ZA
dc.subjectEstrogen Receptor 1 (ESR1)en_ZA
dc.subjectCoiled-coil domain containing 170 (CCDC170)en_ZA
dc.subjectRequired for meiotic nuclear division 1 (RMND1)en_ZA
dc.titleBreast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170en_ZA
dc.typeArticleen_ZA

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