%0 Journal Article
%A Baxter, Joseph S
%A Johnson, Nichola
%A Tomczyk, Katarzyna
%A Gillespie, Andrea
%A Maguire, Sarah
%A Brough, Rachel
%A Fachal, Laura
%A Michailidou, Kyriaki
%A Bolla, Manjeet K
%A Wang, Qin
%A Dennis, Joe
%A Ahearn, Thomas U
%A Andrulis, Irene L
%A Anton-Culver, Hoda
%A Antonenkova, Natalia N
%A Arndt, Volker
%A Aronson, Kristan J
%A Augustinsson, Annelie
%A Becher, Heiko
%A Beckmann, Matthias W
%A Behrens, Sabine
%A Benitez, Javier
%A Bermisheva, Marina
%A Bogdanova, Natalia V
%A Bojesen, Stig E
%A Brenner, Hermann
%A Brucker, Sara Y
%A Cai, Qiuyin
%A Campa, Daniele
%A Canzian, Federico
%A Castelao, Jose E
%A Chan, Tsun L
%A Chang-Claude, Jenny
%A Chanock, Stephen J
%A Chenevix-Trench, Georgia
%A Choi, Ji-Yeob
%A Clarke, Christine L
%A Colonna, Sarah
%A Conroy, Don M
%A Couch, Fergus J
%A Cox, Angela
%A Cross, Simon S
%A Czene, Kamila
%A Daly, Mary B
%A Devilee, Peter
%A Dörk, Thilo
%A Dossus, Laure
%A Dwek, Miriam
%A Eccles, Diana M
%A Ekici, Arif B
%A Eliassen, A Heather
%A Engel, Christoph
%A Fasching, Peter A
%A Figueroa, Jonine
%A Flyger, Henrik
%A Gago-Dominguez, Manuela
%A Gao, Chi
%A García-Closas, Montserrat
%A García-Sáenz, José A
%A Ghoussaini, Maya
%A Giles, Graham G
%A Goldberg, Mark S
%A González-Neira, Anna
%A Guénel, Pascal
%A Gündert, Melanie
%A Haeberle, Lothar
%A Hahnen, Eric
%A Haiman, Christopher A
%A Hall, Per
%A Hamann, Ute
%A Hartman, Mikael
%A Hatse, Sigrid
%A Hauke, Jan
%A Hollestelle, Antoinette
%A Hoppe, Reiner
%A Hopper, John L
%A Hou, Ming-Feng
%A Ito, Hidemi
%A Iwasaki, Motoki
%A Jager, Agnes
%A Jakubowska, Anna
%A Janni, Wolfgang
%A John, Esther M
%A Joseph, Vijai
%A Jung, Audrey
%A Kaaks, Rudolf
%A Kang, Daehee
%A Keeman, Renske
%A Khusnutdinova, Elza
%A Kim, Sung-Won
%A Kosma, Veli-Matti
%A Kraft, Peter
%A Kristensen, Vessela N
%A Kubelka-Sabit, Katerina
%A Kurian, Allison W
%A Kwong, Ava
%A Lacey, James V
%A Lambrechts, Diether
%A Larson, Nicole L
%A Larsson, Susanna C
%A Le Marchand, Loic
%A Lejbkowicz, Flavio
%A Li, Jingmei
%A Long, Jirong
%A Lophatananon, Artitaya
%A Lubiński, Jan
%A Mannermaa, Arto
%A Manoochehri, Mehdi
%A Manoukian, Siranoush
%A Margolin, Sara
%A Matsuo, Keitaro
%A Mavroudis, Dimitrios
%A Mayes, Rebecca
%A Menon, Usha
%A Milne, Roger L
%A Mohd Taib, Nur Aishah
%A Muir, Kenneth
%A Muranen, Taru A
%A Murphy, Rachel A
%A Nevanlinna, Heli
%A O'Brien, Katie M
%A Offit, Kenneth
%A Olson, Janet E
%A Olsson, Håkan
%A Park, Sue K
%A Park-Simon, Tjoung-Won
%A Patel, Alpa V
%A Peterlongo, Paolo
%A Peto, Julian
%A Plaseska-Karanfilska, Dijana
%A Presneau, Nadege
%A Pylkäs, Katri
%A Rack, Brigitte
%A Rennert, Gad
%A Romero, Atocha
%A Ruebner, Matthias
%A Rüdiger, Thomas
%A Saloustros, Emmanouil
%A Sandler, Dale P
%A Sawyer, Elinor J
%A Schmidt, Marjanka K
%A Schmutzler, Rita K
%A Schneeweiss, Andreas
%A Schoemaker, Minouk J
%A Shah, Mitul
%A Shen, Chen-Yang
%A Shu, Xiao-Ou
%A Simard, Jacques
%A Southey, Melissa C
%A Stone, Jennifer
%A Surowy, Harald
%A Swerdlow, Anthony J
%A Tamimi, Rulla M
%A Tapper, William J
%A Taylor, Jack A
%A Teo, Soo Hwang
%A Teras, Lauren R
%A Terry, Mary Beth
%A Toland, Amanda E
%A Tomlinson, Ian
%A Truong, Thérèse
%A Tseng, Chiu-Chen
%A Untch, Michael
%A Vachon, Celine M
%A van den Ouweland, Ans M W
%A Wang, Sophia S
%A Weinberg, Clarice R
%A Wendt, Camilla
%A Winham, Stacey J
%A Winqvist, Robert
%A Wolk, Alicja
%A Wu, Anna H
%A Yamaji, Taiki
%A Zheng, Wei
%A Ziogas, Argyrios
%A Pharoah, Paul D P
%A Dunning, Alison M
%A Easton, Douglas F
%A Pettitt, Stephen J
%A Lord, Christopher J
%A Haider, Syed
%A Orr, Nick
%A Fletcher, Olivia
%T Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.
%J The American journal of human genetics
%V 108
%N 7
%@ 0002-9297
%C New York, NY
%I Elsevier
%M DKFZ-2021-01388
%P 1190-1203
%D 2021
%Z 2021 Jul 1;108(7):1190-1203
%X A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95
%K breast cancer risk (Other)
%K functional annotation (Other)
%K risk locus (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34146516
%R 10.1016/j.ajhg.2021.05.013
%U https://inrepo02.dkfz.de/record/169291