dc.contributor.author | Baxter, JS | |
dc.contributor.author | Johnson, N | |
dc.contributor.author | Tomczyk, K | |
dc.contributor.author | Gillespie, A | |
dc.contributor.author | Maguire, S | |
dc.contributor.author | Brough, R | |
dc.contributor.author | Fachal, L | |
dc.contributor.author | Michailidou, K | |
dc.contributor.author | Bolla, MK | |
dc.contributor.author | Wang, Q | |
dc.contributor.author | Dennis, J | |
dc.contributor.author | Ahearn, TU | |
dc.contributor.author | Andrulis, IL | |
dc.contributor.author | Anton-Culver, H | |
dc.contributor.author | Antonenkova, NN | |
dc.contributor.author | Arndt, V | |
dc.contributor.author | Aronson, KJ | |
dc.contributor.author | Augustinsson, A | |
dc.contributor.author | Becher, H | |
dc.contributor.author | Beckmann, MW | |
dc.contributor.author | Behrens, S | |
dc.contributor.author | Benitez, J | |
dc.contributor.author | Bermisheva, M | |
dc.contributor.author | Bogdanova, NV | |
dc.contributor.author | Bojesen, SE | |
dc.contributor.author | Brenner, H | |
dc.contributor.author | Brucker, SY | |
dc.contributor.author | Cai, Q | |
dc.contributor.author | Campa, D | |
dc.contributor.author | Canzian, F | |
dc.contributor.author | Castelao, JE | |
dc.contributor.author | Chan, TL | |
dc.contributor.author | Chang-Claude, J | |
dc.contributor.author | Chanock, SJ | |
dc.contributor.author | Chenevix-Trench, G | |
dc.contributor.author | Choi, J-Y | |
dc.contributor.author | Clarke, CL | |
dc.contributor.author | NBCS Collaborators, | |
dc.contributor.author | Colonna, S | |
dc.contributor.author | Conroy, DM | |
dc.contributor.author | Couch, FJ | |
dc.contributor.author | Cox, A | |
dc.contributor.author | Cross, SS | |
dc.contributor.author | Czene, K | |
dc.contributor.author | Daly, MB | |
dc.contributor.author | Devilee, P | |
dc.contributor.author | Dörk, T | |
dc.contributor.author | Dossus, L | |
dc.contributor.author | Dwek, M | |
dc.contributor.author | Eccles, DM | |
dc.contributor.author | Ekici, AB | |
dc.contributor.author | Eliassen, AH | |
dc.contributor.author | Engel, C | |
dc.contributor.author | Fasching, PA | |
dc.contributor.author | Figueroa, J | |
dc.contributor.author | Flyger, H | |
dc.contributor.author | Gago-Dominguez, M | |
dc.contributor.author | Gao, C | |
dc.contributor.author | García-Closas, M | |
dc.contributor.author | García-Sáenz, JA | |
dc.contributor.author | Ghoussaini, M | |
dc.contributor.author | Giles, GG | |
dc.contributor.author | Goldberg, MS | |
dc.contributor.author | González-Neira, A | |
dc.contributor.author | Guénel, P | |
dc.contributor.author | Gündert, M | |
dc.contributor.author | Haeberle, L | |
dc.contributor.author | Hahnen, E | |
dc.contributor.author | Haiman, CA | |
dc.contributor.author | Hall, P | |
dc.contributor.author | Hamann, U | |
dc.contributor.author | Hartman, M | |
dc.contributor.author | Hatse, S | |
dc.contributor.author | Hauke, J | |
dc.contributor.author | Hollestelle, A | |
dc.contributor.author | Hoppe, R | |
dc.contributor.author | Hopper, JL | |
dc.contributor.author | Hou, M-F | |
dc.contributor.author | kConFab Investigators, | |
dc.contributor.author | ABCTB Investigators, | |
dc.contributor.author | Ito, H | |
dc.contributor.author | Iwasaki, M | |
dc.contributor.author | Jager, A | |
dc.contributor.author | Jakubowska, A | |
dc.contributor.author | Janni, W | |
dc.contributor.author | John, EM | |
dc.contributor.author | Joseph, V | |
dc.contributor.author | Jung, A | |
dc.contributor.author | Kaaks, R | |
dc.contributor.author | Kang, D | |
dc.contributor.author | Keeman, R | |
dc.contributor.author | Khusnutdinova, E | |
dc.contributor.author | Kim, S-W | |
dc.contributor.author | Kosma, V-M | |
dc.contributor.author | Kraft, P | |
dc.contributor.author | Kristensen, VN | |
dc.contributor.author | Kubelka-Sabit, K | |
dc.contributor.author | Kurian, AW | |
dc.contributor.author | Kwong, A | |
dc.contributor.author | Lacey, JV | |
dc.contributor.author | Lambrechts, D | |
dc.contributor.author | Larson, NL | |
dc.contributor.author | Larsson, SC | |
dc.contributor.author | Le Marchand, L | |
dc.contributor.author | Lejbkowicz, F | |
dc.contributor.author | Li, J | |
dc.contributor.author | Long, J | |
dc.contributor.author | Lophatananon, A | |
dc.contributor.author | Lubiński, J | |
dc.contributor.author | Mannermaa, A | |
dc.contributor.author | Manoochehri, M | |
dc.contributor.author | Manoukian, S | |
dc.contributor.author | Margolin, S | |
dc.contributor.author | Matsuo, K | |
dc.contributor.author | Mavroudis, D | |
dc.contributor.author | Mayes, R | |
dc.contributor.author | Menon, U | |
dc.contributor.author | Milne, RL | |
dc.contributor.author | Mohd Taib, NA | |
dc.contributor.author | Muir, K | |
dc.contributor.author | Muranen, TA | |
dc.contributor.author | Murphy, RA | |
dc.contributor.author | Nevanlinna, H | |
dc.contributor.author | O'Brien, KM | |
dc.contributor.author | Offit, K | |
dc.contributor.author | Olson, JE | |
dc.contributor.author | Olsson, H | |
dc.contributor.author | Park, SK | |
dc.contributor.author | Park-Simon, T-W | |
dc.contributor.author | Patel, AV | |
dc.contributor.author | Peterlongo, P | |
dc.contributor.author | Peto, J | |
dc.contributor.author | Plaseska-Karanfilska, D | |
dc.contributor.author | Presneau, N | |
dc.contributor.author | Pylkäs, K | |
dc.contributor.author | Rack, B | |
dc.contributor.author | Rennert, G | |
dc.contributor.author | Romero, A | |
dc.contributor.author | Ruebner, M | |
dc.contributor.author | Rüdiger, T | |
dc.contributor.author | Saloustros, E | |
dc.contributor.author | Sandler, DP | |
dc.contributor.author | Sawyer, EJ | |
dc.contributor.author | Schmidt, MK | |
dc.contributor.author | Schmutzler, RK | |
dc.contributor.author | Schneeweiss, A | |
dc.contributor.author | Schoemaker, MJ | |
dc.contributor.author | Shah, M | |
dc.contributor.author | Shen, C-Y | |
dc.contributor.author | Shu, X-O | |
dc.contributor.author | Simard, J | |
dc.contributor.author | Southey, MC | |
dc.contributor.author | Stone, J | |
dc.contributor.author | Surowy, H | |
dc.contributor.author | Swerdlow, AJ | |
dc.contributor.author | Tamimi, RM | |
dc.contributor.author | Tapper, WJ | |
dc.contributor.author | Taylor, JA | |
dc.contributor.author | Teo, SH | |
dc.contributor.author | Teras, LR | |
dc.contributor.author | Terry, MB | |
dc.contributor.author | Toland, AE | |
dc.contributor.author | Tomlinson, I | |
dc.contributor.author | Truong, T | |
dc.contributor.author | Tseng, C-C | |
dc.contributor.author | Untch, M | |
dc.contributor.author | Vachon, CM | |
dc.contributor.author | van den Ouweland, AMW | |
dc.contributor.author | Wang, SS | |
dc.contributor.author | Weinberg, CR | |
dc.contributor.author | Wendt, C | |
dc.contributor.author | Winham, SJ | |
dc.contributor.author | Winqvist, R | |
dc.contributor.author | Wolk, A | |
dc.contributor.author | Wu, AH | |
dc.contributor.author | Yamaji, T | |
dc.contributor.author | Zheng, W | |
dc.contributor.author | Ziogas, A | |
dc.contributor.author | Pharoah, PDP | |
dc.contributor.author | Dunning, AM | |
dc.contributor.author | Easton, DF | |
dc.contributor.author | Pettitt, SJ | |
dc.contributor.author | Lord, CJ | |
dc.contributor.author | Haider, S | |
dc.contributor.author | Orr, N | |
dc.contributor.author | Fletcher, O | |
dc.date.accessioned | 2021-07-28T10:30:20Z | |
dc.date.available | 2021-07-28T10:30:20Z | |
dc.date.issued | 2021-07-01 | |
dc.identifier.citation | American journal of human genetics, 2021, 108 (7), pp. 1190 - 1203 | |
dc.identifier.issn | 0002-9297 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4704 | |
dc.identifier.eissn | 1537-6605 | |
dc.identifier.doi | 10.1016/j.ajhg.2021.05.013 | |
dc.description.abstract | 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% CI 0.74-0.81, p = 3.1 × 10-31). | |
dc.format | Print-Electronic | |
dc.format.extent | 1190 - 1203 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | NBCS Collaborators | |
dc.subject | kConFab Investigators | |
dc.subject | ABCTB Investigators | |
dc.title | Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-05-25 | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1016/j.ajhg.2021.05.013 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | American journal of human genetics | |
pubs.issue | 7 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genetic Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genetic Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function | |
pubs.publication-status | Published | |
pubs.volume | 108 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Functional Genetic Epidemiology | |
icr.researchteam | Aetiological Epidemiology | |
icr.researchteam | Gene Function | |
icr.researchteam | Functional Genetic Epidemiology | |
icr.researchteam | Aetiological Epidemiology | |
icr.researchteam | Gene Function | |
dc.contributor.icrauthor | Schoemaker, Minouk | |
dc.contributor.icrauthor | Swerdlow, Anthony | |
dc.contributor.icrauthor | Pettitt, Stephen | |
dc.contributor.icrauthor | Lord, Christopher | |
dc.contributor.icrauthor | Haider, Syed | |
dc.contributor.icrauthor | Fletcher, Olivia | |