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Association analysis identifies 65 new breast cancer risk loci.

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Date
2017-11
ICR Author
Fletcher, Olivia
Orr, Nicholas
Schoemaker, Minouk
Jones, Michael
Swerdlow, Anthony
Author
Michailidou, K
Lindström, S
Dennis, J
Beesley, J
Hui, S
Kar, S
Lemaçon, A
Soucy, P
Glubb, D
Rostamianfar, A
Bolla, MK
Wang, Q
Tyrer, J
Dicks, E
Lee, A
Wang, Z
Allen, J
Keeman, R
Eilber, U
French, JD
Qing Chen, X
Fachal, L
McCue, K
McCart Reed, AE
Ghoussaini, M
Carroll, JS
Jiang, X
Finucane, H
Adams, M
Adank, MA
Ahsan, H
Aittomäki, K
Anton-Culver, H
Antonenkova, NN
Arndt, V
Aronson, KJ
Arun, B
Auer, PL
Bacot, F
Barrdahl, M
Baynes, C
Beckmann, MW
Behrens, S
Benitez, J
Bermisheva, M
Bernstein, L
Blomqvist, C
Bogdanova, NV
Bojesen, SE
Bonanni, B
Børresen-Dale, A-L
Brand, JS
Brauch, H
Brennan, P
Brenner, H
Brinton, L
Broberg, P
Brock, IW
Broeks, A
Brooks-Wilson, A
Brucker, SY
Brüning, T
Burwinkel, B
Butterbach, K
Cai, Q
Cai, H
Caldés, T
Canzian, F
Carracedo, A
Carter, BD
Castelao, JE
Chan, TL
David Cheng, T-Y
Seng Chia, K
Choi, J-Y
Christiansen, H
Clarke, CL
NBCS Collaborators
Collée, M
Conroy, DM
Cordina-Duverger, E
Cornelissen, S
Cox, DG
Cox, A
Cross, SS
Cunningham, JM
Czene, K
Daly, MB
Devilee, P
Doheny, KF
Dörk, T
Dos-Santos-Silva, I
Dumont, M
Durcan, L
Dwek, M
Eccles, DM
Ekici, AB
Eliassen, AH
Ellberg, C
Elvira, M
Engel, C
Eriksson, M
Fasching, PA
Figueroa, J
Flesch-Janys, D
Fletcher, O
Flyger, H
Fritschi, L
Gaborieau, V
Gabrielson, M
Gago-Dominguez, M
Gao, Y-T
Gapstur, SM
García-Sáenz, JA
Gaudet, MM
Georgoulias, V
Giles, GG
Glendon, G
Goldberg, MS
Goldgar, DE
González-Neira, A
Grenaker Alnæs, GI
Grip, M
Gronwald, J
Grundy, A
Guénel, P
Haeberle, L
Hahnen, E
Haiman, CA
Håkansson, N
Hamann, U
Hamel, N
Hankinson, S
Harrington, P
Hart, SN
Hartikainen, JM
Hartman, M
Hein, A
Heyworth, J
Hicks, B
Hillemanns, P
Ho, DN
Hollestelle, A
Hooning, MJ
Hoover, RN
Hopper, JL
Hou, M-F
Hsiung, C-N
Huang, G
Humphreys, K
Ishiguro, J
Ito, H
Iwasaki, M
Iwata, H
Jakubowska, A
Janni, W
John, EM
Johnson, N
Jones, K
Jones, M
Jukkola-Vuorinen, A
Kaaks, R
Kabisch, M
Kaczmarek, K
Kang, D
Kasuga, Y
Kerin, MJ
Khan, S
Khusnutdinova, E
Kiiski, JI
Kim, S-W
Knight, JA
Kosma, V-M
Kristensen, VN
Krüger, U
Kwong, A
Lambrechts, D
Le Marchand, L
Lee, E
Lee, MH
Lee, JW
Neng Lee, C
Lejbkowicz, F
Li, J
Lilyquist, J
Lindblom, A
Lissowska, J
Lo, W-Y
Loibl, S
Long, J
Lophatananon, A
Lubinski, J
Luccarini, C
Lux, MP
Ma, ESK
MacInnis, RJ
Maishman, T
Makalic, E
Malone, KE
Kostovska, IM
Mannermaa, A
Manoukian, S
Manson, JE
Margolin, S
Mariapun, S
Martinez, ME
Matsuo, K
Mavroudis, D
McKay, J
McLean, C
Meijers-Heijboer, H
Meindl, A
Menéndez, P
Menon, U
Meyer, J
Miao, H
Miller, N
Taib, NAM
Muir, K
Mulligan, AM
Mulot, C
Neuhausen, SL
Nevanlinna, H
Neven, P
Nielsen, SF
Noh, D-Y
Nordestgaard, BG
Norman, A
Olopade, OI
Olson, JE
Olsson, H
Olswold, C
Orr, N
Pankratz, VS
Park, SK
Park-Simon, T-W
Lloyd, R
Perez, JIA
Peterlongo, P
Peto, J
Phillips, K-A
Pinchev, M
Plaseska-Karanfilska, D
Prentice, R
Presneau, N
Prokofyeva, D
Pugh, E
Pylkäs, K
Rack, B
Radice, P
Rahman, N
Rennert, G
Rennert, HS
Rhenius, V
Romero, A
Romm, J
Ruddy, KJ
Rüdiger, T
Rudolph, A
Ruebner, M
Rutgers, EJT
Saloustros, E
Sandler, DP
Sangrajrang, S
Sawyer, EJ
Schmidt, DF
Schmutzler, RK
Schneeweiss, A
Schoemaker, MJ
Schumacher, F
Schürmann, P
Scott, RJ
Scott, C
Seal, S
Seynaeve, C
Shah, M
Sharma, P
Shen, C-Y
Sheng, G
Sherman, ME
Shrubsole, MJ
Shu, X-O
Smeets, A
Sohn, C
Southey, MC
Spinelli, JJ
Stegmaier, C
Stewart-Brown, S
Stone, J
Stram, DO
Surowy, H
Swerdlow, A
Tamimi, R
Taylor, JA
Tengström, M
Teo, SH
Beth Terry, M
Tessier, DC
Thanasitthichai, S
Thöne, K
Tollenaar, RAEM
Tomlinson, I
Tong, L
Torres, D
Truong, T
Tseng, C-C
Tsugane, S
Ulmer, H-U
Ursin, G
Untch, M
Vachon, C
van Asperen, CJ
Van Den Berg, D
van den Ouweland, AMW
van der Kolk, L
van der Luijt, RB
Vincent, D
Vollenweider, J
Waisfisz, Q
Wang-Gohrke, S
Weinberg, CR
Wendt, C
Whittemore, AS
Wildiers, H
Willett, W
Winqvist, R
Wolk, A
Wu, AH
Xia, L
Yamaji, T
Yang, XR
Har Yip, C
Yoo, K-Y
Yu, J-C
Zheng, W
Zheng, Y
Zhu, B
Ziogas, A
Ziv, E
ABCTB Investigators
ConFab/AOCS Investigators
Lakhani, SR
Antoniou, AC
Droit, A
Andrulis, IL
Amos, CI
Couch, FJ
Pharoah, PDP
Chang-Claude, J
Hall, P
Hunter, DJ
Milne, RL
García-Closas, M
Schmidt, MK
Chanock, SJ
Dunning, AM
Edwards, SL
Bader, GD
Chenevix-Trench, G
Simard, J
Kraft, P
Easton, DF
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Type
Journal Article
Metadata
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Abstract
Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10 -8 . The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
URI
https://repository.icr.ac.uk/handle/internal/2042
DOI
https://doi.org/10.1038/nature24284
Collections
  • Breast Cancer Research
  • Genetics and Epidemiology
Subject
NBCS Collaborators
ABCTB Investigators
ConFab/AOCS Investigators
Humans
Breast Neoplasms
Genetic Predisposition to Disease
Transcription Factors
Risk Assessment
Binding Sites
Regulatory Sequences, Nucleic Acid
Multifactorial Inheritance
Polymorphism, Single Nucleotide
Computer Simulation
Asian Continental Ancestry Group
European Continental Ancestry Group
Asia
Europe
Female
Genome-Wide Association Study
Genetic Loci
Research team
Complex Trait Genetics
Functional Genetic Epidemiology
Aetiological Epidemiology
Language
eng
Date accepted
2017-09-17
License start date
2017-11
Citation
Nature, 2017, 551 (7678), pp. 92 - 94

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