Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.
Nature Publishing Group, 2016
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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
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Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.
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| Autor/in / Beteiligte Person: | Dunning, Alison M ; Michailidou, Kyriaki ; Kuchenbaecker, Karoline B ; Thompson, Deborah ; French, Juliet D ; Beesley, Jonathan ; Healey, Catherine S ; Kar, Siddhartha ; Pooley, Karen A ; Lopez-Knowles, Elena ; Dicks, Ed ; Gronwald, Jacek ; Huzarski, Tomasz ; Barkardottir, Rosa B ; Laframboise, Rachel ; Soucy, Penny ; Montagna, Marco ; Agata, Simona ; Teixeira, Manuel R ; Park, Sue Kyung ; Hills, Margaret ; Cox, Angela ; Lindor, Noralane ; Couch, Fergus J ; Tischkowitz, Marc ; Foretova, Lenka ; Vijai, Joseph ; Offit, Kenneth ; Singer, Christian F ; Rappaport, Christine ; Phelan, Catherine M ; Greene, Mark H ; Cross, Simon S ; Jarosz, Monika ; Mai, Phuong L ; Rennert, Gad ; Imyanitov, Evgeny N ; Hulick, Peter J ; Phillips, Kelly-Anne ; Piedmonte, Marion ; Mulligan, Anna Marie ; Glendon, Gord ; Bojesen, Anders ; Blot, William ; Thomassen, Mads ; Drury, Suzie ; Caligo, Maria A ; Yoon, Sook-Yee ; Friedman, Eitan ; Laitman, Yael ; Borg, Ake ; von Wachenfeldt, Anna ; Ehrencrona, Hans ; Rantala, Johanna ; Cai, Qiuyin ; Olopade, Olufunmilayo I ; Ganz, Patricia A ; Canisius, Sander ; Nussbaum, Robert L ; Gayther, Simon A ; Nathanson, Katherine L ; Domchek, Susan M ; Arun, Banu K ; Mitchell, Gillian ; Karlan, Beth Y ; Ghoussaini, Maya ; Lester, Jenny ; Maskarinec, Gertraud ; Woolcott, Christy ; Bolla, Manjeet K ; Scott, Christopher ; Stone, Jennifer ; Apicella, Carmel ; Tamimi, Rulla ; Luben, Robert ; Khaw, Kay-Tee ; Perkins, Barbara J ; Helland, Åslaug ; Haakensen, Vilde ; Dowsett, Mitch ; Pharoah, Paul D P ; Dennis, Joe ; Simard, Jacques ; Hall, Per ; García-Closas, Montserrat ; Vachon, Celine ; Chenevix-Trench, Georgia ; Shah, Mitul ; Antoniou, Antonis C ; Easton, Douglas F ; Edwards, Stacey L ; Wang, Qin ; Hopper, John L ; Southey, Melissa C ; Broeks, Annegien ; Schmidt, Marjanka K ; Lophatananon, Artitaya ; Muir, Kenneth ; Choi, Ji-Yeob ; Beckmann, Matthias W ; Fasching, Peter A ; Dos-Santos-Silva, Isabel ; Peto, Julian ; Sawyer, Elinor J ; Tomlinson, Ian ; Burwinkel, Barbara ; Marme, Frederik ; Guénel, Pascal ; Truong, Thérèse ; Kang, Daehee ; Bojesen, Stig E ; Flyger, Henrik ; González-Neira, Anna ; Perez, Jose I A ; Anton-Culver, Hoda ; Eunjung, Lee ; Arndt, Volker ; Brenner, Hermann ; Meindl, Alfons ; Schmutzler, Rita K ; Lee, Soo Chin ; Brauch, Hiltrud ; Hamann, Ute ; Aittomäki, Kristiina ; Blomqvist, Carl ; Ito, Hidemi ; Matsuo, Keitaro ; Bogdanova, Natasha ; Dörk, Thilo ; Lindblom, Annika ; Margolin, Sara ; Barrowdale, Daniel ; Kosma, Veli-Matti ; Mannermaa, Arto ; Tseng, Chiu-Chen ; Wu, Anna H ; Lambrechts, Diether ; Wildiers, Hans ; Chang-Claude, Jenny ; Rudolph, Anja ; Peterlongo, Paolo ; Radice, Paolo ; Hartman, Mikael ; Olson, Janet E ; Giles, Graham G ; Milne, Roger L ; Haiman, Christopher A ; Henderson, Brian E ; Goldberg, Mark S ; Teo, Soo H ; Yip, Cheng Har ; Nord, Silje ; Borresen-Dale, Anne-Lise ; Kabisch, Maria ; Kristensen, Vessela ; Long, Jirong ; Zheng, Wei ; Pylkäs, Katri ; Winqvist, Robert ; Andrulis, Irene L ; Knight, Julia A ; Devilee, Peter ; Seynaeve, Caroline ; Figueroa, Jonine ; Torres, Diana ; Sherman, Mark E ; Czene, Kamila ; Darabi, Hatef ; Hollestelle, Antoinette ; van den Ouweland, Ans M W ; Humphreys, Keith ; Gao, Yu-Tang ; Shu, Xiao-Ou ; Jakubowska, Anna ; Lubinski, Jan ; Brennan, Paul ; Sangrajrang, Suleeporn ; Ambrosone, Christine B ; Toland, Amanda E ; Shen, Chen-Yang ; Sinnott-Armstrong, Nicholas A ; Wu, Pei-Ei ; Orr, Nick ; Swerdlow, Anthony ; McGuffog, Lesley ; Healey, Sue ; Lee, Andrew ; Kapuscinski, Miroslav ; John, Esther M ; Terry, Mary Beth ; Daly, Mary B ; Sallari, Richard C ; Goldgar, David E ; Buys, Saundra S ; Janavicius, Ramunas ; Tihomirova, Laima ; Tung, Nadine ; Dorfling, Cecilia M ; van Rensburg, Elizabeth J ; Neuhausen, Susan L ; Ejlertsen, Bent ; Hansen, Thomas V O ; Hillman, Kristine M ; Osorio, Ana ; Benitez, Javier ; Rando, Rachel ; Weitzel, Jeffrey N ; Bonanni, Bernardo ; Peissel, Bernard ; Manoukian, Siranoush ; Papi, Laura ; Ottini, Laura ; Konstantopoulou, Irene ; Kaufmann, Susanne ; Apostolou, Paraskevi ; Garber, Judy ; Rashid, Muhammad Usman ; Frost, Debra ; Izatt, Louise ; Ellis, Steve ; Godwin, Andrew K ; Arnold, Norbert ; Niederacher, Dieter ; Rhiem, Kerstin ; Sivakumaran, Haran ; Bogdanova-Markov, Nadja ; Sagne, Charlotte ; Stoppa-Lyonnet, Dominique ; Damiola, Francesca ; Sinilnikova, Olga M ; Mazoyer, Sylvie ; Isaacs, Claudine ; Claes, Kathleen B M ; De Leeneer, Kim ; de la Hoya, Miguel ; Moradi Marjaneh, Mahdi ; Caldes, Trinidad ; Nevanlinna, Heli ; Khan, Sofia ; Mensenkamp, Arjen R ; Hooning, Maartje J ; Rookus, Matti A ; Kwong, Ava ; Olah, Edith ; Diez, Orland ; Brunet, Joan ; Lee, Jason S ; Pujana, Miquel Angel ; 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, 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Immunol Genet & Pathol, Uppsala, Sweden 188 Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden 189 Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden 190 Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA 191 Univ Calif Los Angeles, Sch Med, Johnsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA 192 Univ Calif Los Angeles, Sch Publ Hlth, Johnsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA 193 Univ Calif San Francisco, Dept Med & Genet, San Francisco, CA 94143 USA 194 Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA 195 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA 196 Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic, Australia 197 Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia 198 Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA 199 Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA 200 Dalhousie Univ, Dept Obstet Gynaecol & Pediat, Halifax, NS, Canada 201 Univ Western Australia, Ctr Genet Origins Hlth & Dis, Perth, WA 6009, Australia 202 Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA 203 Harvard Univ, Sch Med, Boston, MA USA 204 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA 205 Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, 665 Huntington Ave, Boston, MA 02115 USA 206 Univ Cambridge, Dept Publ Hlth & Primary Care, Clin Gerontol, Cambridge, England |
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| Veröffentlichung: | Nature Publishing Group, 2016 |
| Medientyp: | academicJournal |
| ISSN: | 1546-1718 (print) |
| DOI: | 10.1038/ng.3521 |
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