학술논문
Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170
Document Type
Author
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; Barrowdale, Daniel; Sinnott-Armstrong, Nicholas A.; Sallari, Richard C.; Hillman, Kristine M.; Kaufmann, Susanne; Sivakumaran, Haran; Marjaneh, Mahdi Moradi; Lee, Jason S.; Hills, Margaret; Jarosz, Monika; Drury, Suzie; Canisius, Sander; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Hopper, John L.; Southey, Melissa C.; Broeks, Annegien; Schmidt, Marjanka K.; Lophatananon, Artitaya; Muir, Kenneth; Beckmann, Matthias W.; Fasching, Peter A.; dos-Santos-Silva, Isabel; Peto, Julian; Sawyer, Elinor J.; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guenel, Pascal; Truong, Therese; Bojesen, Stig E.; Flyger, Henrik; Gonzalez-Neira, Anna; Perez, Jose I. A.; Anton-Culver, Hoda; Eunjung, Lee; Arndt, Volker; Brenner, Hermann; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Hamann, Ute; Aittomaki, Kristiina; Blomqvist, Carl; Ito, Hidemi; Matsuo, Keitaro; Bogdanova, Natasha; Dork, Thilo; Lindblom, Annika; Margolin, Sara; Kosma, Veli-Matti; Mannermaa, Arto; Tseng, Chiu-chen; Wu, Anna H.; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Rudolph, Anja; Peterlongo, Paolo; Radice, Paolo; 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; Kristensen, Vessela; Long, Jirong; Zheng, Wei; Pylkas, Katri; Winqvist, Robert; Andrulis, Irene L.; Knight, Julia A.; Devilee, Peter; Seynaeve, Caroline; Figueroa, Jonine; Sherman, Mark E.; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Humphreys, Keith; Gao, Yu-Tang; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S.; Blot, William; Cai, Qiuyin; Ghoussaini, Maya; Perkins, Barbara J.; Shah, Mitul; Choi, Ji-Yeob; Kang, Daehee; Lee, Soo Chin; Hartman, Mikael; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Brennan, Paul; Sangrajrang, Suleeporn; Ambrosone, Christine B.; Toland, Amanda E.; Shen, Chen-Yang; Wu, Pei-Ei; Orr, Nick; Swerdlow, Anthony; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Kapuscinski, Miroslav; John, Esther M.; Terry, Mary Beth; Daly, Mary B.; 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.; Osorio, Ana; Benitez, Javier; Rando, Rachel; Weitzel, Jeffrey N.; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Papi, Laura; Ottini, Laura; Konstantopoulou, Irene; Apostolou, Paraskevi; Garber, Judy; Rashid, Muhammad Usman; Frost, Debra; Izatt, Louise; Ellis, Steve; Godwin, Andrew K.; Arnold, Norbert; Niederacher, Dieter; Rhiem, Kerstin; 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; Caldes, Trinidad; Nevanlinna, Heli; Khan, Sofia; Mensenkamp, Arjen R.; Hooning, Maartje J.; Rookus, Matti A.; Kwong, Ava; Olah, Edith; Diez, Orland; Brunet, Joan; Pujana, Miquel Angel; Gronwald, Jacek; Huzarski, Tomasz; Barkardottir, Rosa B.; Laframboise, Rachel; Soucy, Penny; Montagna, Marco; Agata, Simona; Teixeira, Manuel R.; Park, Sue Kyung; Lindor, Noralane; Couch, Fergus J.; Tischkowitz, Marc; Foretova, Lenka; Vijai, Joseph; Offit, Kenneth; Singer, Christian F.; Rappaport, Christine; Phelan, Catherine M.; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Imyanitov, Evgeny N.; Hulick, Peter J.; Phillips, Kelly-Anne; Piedmonte, Marion; Mulligan, Anna Marie; Glendon, Gord; Bojesen, Anders; Thomassen, Mads; Caligo, Maria A.; Yoon, Sook-Yee; Friedman, Eitan; Laitman, Yael; Borg, Ake; Von Wachenfeldt, Anna; Ehrencrona, Hans; Rantala, Johanna; Olopade, Olufunmilayo I.; Ganz, Patricia A.; Nussbaum, Robert L.; Gayther, Simon A.; Nathanson, Katherine L.; Domchek, Susan M.; Arun, Banu K.; Mitchell, Gillian; Karlan, Beth Y.; Lester, Jenny; Maskarinec, Gertraud; Woolcott, Christy; Scott, Christopher; Stone, Jennifer; Apicella, Carmel; Tamimi, Rulla; Luben, Robert; Khaw, Kay-Tee; Helland, Aslaug; Haakensen, Vilde; Dowsett, Mitch; Pharoah, Paul D. P.; Simard, Jacques; Hall, Per; Garcia-Closas, Montserrat; Vachon, Celine; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Easton, Douglas F.; Edwards, Stacey L.
Source
Nature Genetics. 48(4):374-386
Subject
Language
English
ISSN
1061-4036
1546-1718
1546-1718
Abstract
We 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.