Abstract
Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 489-503 |
| Number of pages | 15 |
| Journal | American journal of human genetics |
| Volume | 92 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 4 2013 |
| Externally published | Yes |
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Access to Document
Other files and links
Fingerprint
Dive into the research topics of 'Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers'. Together they form a unique fingerprint.Cite this
- APA
- Standard
- Harvard
- Vancouver
- Author
- BIBTEX
- RIS
In: American journal of human genetics, Vol. 92, No. 4, 04.04.2013, p. 489-503.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers
AU - French, Juliet D.
AU - Ghoussaini, Maya
AU - Edwards, Stacey L.
AU - Meyer, Kerstin B.
AU - Michailidou, Kyriaki
AU - Ahmed, Shahana
AU - Khan, Sofia
AU - Maranian, Mel J.
AU - O'Reilly, Martin
AU - Hillman, Kristine M.
AU - Betts, Joshua A.
AU - Carroll, Thomas
AU - Bailey, Peter J.
AU - Dicks, Ed
AU - Beesley, Jonathan
AU - Tyrer, Jonathan
AU - Maia, Ana Teresa
AU - Beck, Andrew
AU - Knoblauch, Nicholas W.
AU - Chen, Constance
AU - Kraft, Peter
AU - Barnes, Daniel
AU - González-Neira, Anna
AU - Alonso, M. Rosario
AU - Herrero, Daniel
AU - Tessier, Daniel C.
AU - Vincent, Daniel
AU - Bacot, Francois
AU - Luccarini, Craig
AU - Baynes, Caroline
AU - Conroy, Don
AU - Dennis, Joe
AU - Bolla, Manjeet K.
AU - Wang, Qin
AU - Hopper, John L.
AU - Southey, Melissa C.
AU - Schmidt, Marjanka K.
AU - Broeks, Annegien
AU - Verhoef, Senno
AU - Cornelissen, Sten
AU - Muir, Kenneth
AU - Lophatananon, Artitaya
AU - Stewart-Brown, Sarah
AU - Siriwanarangsan, Pornthep
AU - Fasching, Peter A.
AU - Loehberg, Christian R.
AU - Ekici, Arif B.
AU - Beckmann, Matthias W.
AU - Peto, Julian
AU - Dos Santos Silva, Isabel
AU - Johnson, Nichola
AU - Aitken, Zoe
AU - Sawyer, Elinor J.
AU - Tomlinson, Ian
AU - Kerin, Michael J.
AU - Miller, Nicola
AU - Marme, Frederik
AU - Schneeweiss, Andreas
AU - Sohn, Christof
AU - Burwinkel, Barbara
AU - Guénel, Pascal
AU - Truong, Thérèse
AU - Laurent-Puig, Pierre
AU - Menegaux, Florence
AU - Bojesen, Stig E.
AU - Nordestgaard, Børge G.
AU - Nielsen, Sune F.
AU - Flyger, Henrik
AU - Milne, Roger L.
AU - Zamora, M. Pilar
AU - Arias Perez, Jose Ignacio
AU - Benitez, Javier
AU - Anton-Culver, Hoda
AU - Brenner, Hermann
AU - Müller, Heiko
AU - Arndt, Volker
AU - Stegmaier, Christa
AU - Meindl, Alfons
AU - Lichtner, Peter
AU - Schmutzler, Rita K.
AU - Engel, Christoph
AU - Brauch, Hiltrud
AU - Hamann, Ute
AU - Justenhoven, Christina
AU - Aaltonen, Kirsimari
AU - Heikkilä, Päivi
AU - Aittomäki, Kristiina
AU - Blomqvist, Carl
AU - Matsuo, Keitaro
AU - Ito, Hidemi
AU - Iwata, Hiroji
AU - Sueta, Aiko
AU - Bogdanova, Natalia V.
AU - Antonenkova, Natalia N.
AU - Dörk, Thilo
AU - Lindblom, Annika
AU - Margolin, Sara
AU - Mannermaa, Arto
AU - Kataja, Vesa
AU - Kosma, Veli Matti
AU - Hartikainen, Jaana M.
AU - Wu, Anna H.
AU - Tseng, Chiu Chen
AU - Van Den Berg, David
AU - Stram, Daniel O.
AU - Lambrechts, Diether
AU - Peeters, Stephanie
AU - Smeets, Ann
AU - Floris, Giuseppe
AU - Chang-Claude, Jenny
AU - Rudolph, Anja
AU - Nickels, Stefan
AU - Flesch-Janys, Dieter
AU - Radice, Paolo
AU - Peterlongo, Paolo
AU - Bonanni, Bernardo
AU - Sardella, Domenico
AU - Couch, Fergus J.
AU - Wang, Xianshu
AU - Pankratz, Vernon S.
AU - Lee, Adam
AU - Giles, Graham G.
AU - Severi, Gianluca
AU - Baglietto, Laura
AU - Haiman, Christopher A.
AU - Henderson, Brian E.
AU - Schumacher, Fredrick
AU - Le Marchand, Loic
AU - Simard, Jacques
AU - Goldberg, Mark S.
AU - Labrèche, France
AU - Dumont, Martine
AU - Teo, Soo Hwang
AU - Yip, Cheng Har
AU - Ng, Char Hong
AU - Vithana, Eranga Nishanthie
AU - Kristensen, Vessela
AU - Zheng, Wei
AU - Deming-Halverson, Sandra
AU - Shrubsole, Martha
AU - Long, Jirong
AU - Winqvist, Robert
AU - Pylkäs, Katri
AU - Jukkola-Vuorinen, Arja
AU - Grip, Mervi
AU - Andrulis, Irene L.
AU - Knight, Julia A.
AU - Glendon, Gord
AU - Mulligan, Anna Marie
AU - Devilee, Peter
AU - Seynaeve, Caroline
AU - García-Closas, Montserrat
AU - Figueroa, Jonine
AU - Chanock, Stephen J.
AU - Lissowska, Jolanta
AU - Czene, Kamila
AU - Klevebring, Daniel
AU - Schoof, Nils
AU - Hooning, Maartje J.
AU - Martens, John W.M.
AU - Collée, J. Margriet
AU - Tilanus-Linthorst, Madeleine
AU - Hall, Per
AU - Li, Jingmei
AU - Liu, Jianjun
AU - Humphreys, Keith
AU - Shu, Xiao Ou
AU - Lu, Wei
AU - Gao, Yu Tang
AU - Cai, Hui
AU - Cox, Angela
AU - Balasubramanian, Sabapathy P.
AU - Blot, William
AU - Signorello, Lisa B.
AU - Cai, Qiuyin
AU - Pharoah, Paul D.P.
AU - Healey, Catherine S.
AU - Shah, Mitul
AU - Pooley, Karen A.
AU - Kang, Daehee
AU - Yoo, Keun Young
AU - Noh, Dong Young
AU - Hartman, Mikael
AU - Miao, Hui
AU - Sng, Jen Hwei
AU - Sim, Xueling
AU - Jakubowska, Anna
AU - Lubinski, Jan
AU - Jaworska-Bieniek, Katarzyna
AU - Durda, Katarzyna
AU - Sangrajrang, Suleeporn
AU - Gaborieau, Valerie
AU - McKay, James
AU - Toland, Amanda E.
AU - Ambrosone, Christine B.
AU - Yannoukakos, Drakoulis
AU - Godwin, Andrew K.
AU - Shen, Chen Yang
AU - Hsiung, Chia Ni
AU - Wu, Pei Ei
AU - Chen, Shou Tung
AU - Swerdlow, Anthony
AU - Ashworth, Alan
AU - Orr, Nick
AU - Schoemaker, Minouk J.
AU - Ponder, Bruce A.J.
AU - Nevanlinna, Heli
AU - Brown, Melissa A.
AU - Chenevix-Trench, Georgia
AU - Easton, Douglas F.
AU - Dunning, Alison M.
PY - 2013/4/4
Y1 - 2013/4/4
N2 - Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.
AB - Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.
UR - http://www.scopus.com/inward/record.url?scp=84875933011&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875933011&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2013.01.002
DO - 10.1016/j.ajhg.2013.01.002
M3 - Article
C2 - 23540573
AN - SCOPUS:84875933011
SN - 0002-9297
VL - 92
SP - 489
EP - 503
JO - American journal of human genetics
JF - American journal of human genetics
IS - 4
ER -