Rare germline copy number variants (CNVs) and breast cancer risk.
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Date
2022-01-18Author
Dennis, J
Tyrer, JP
Walker, LC
Michailidou, K
Dorling, L
Bolla, MK
Wang, Q
Ahearn, TU
Andrulis, IL
Anton-Culver, H
Antonenkova, NN
Arndt, V
Aronson, KJ
Freeman, LEB
Beckmann, MW
Behrens, S
Benitez, J
Bermisheva, M
Bogdanova, NV
Bojesen, SE
Brenner, H
Castelao, JE
Chang-Claude, J
Chenevix-Trench, G
Clarke, CL
NBCS Collaborators,
Collée, JM
CTS Consortium,
Couch, FJ
Cox, A
Cross, SS
Czene, K
Devilee, P
Dörk, T
Dossus, L
Eliassen, AH
Eriksson, M
Evans, DG
Fasching, PA
Figueroa, J
Fletcher, O
Flyger, H
Fritschi, L
Gabrielson, M
Gago-Dominguez, M
García-Closas, M
Giles, GG
González-Neira, A
Guénel, P
Hahnen, E
Haiman, CA
Hall, P
Hollestelle, A
Hoppe, R
Hopper, JL
Howell, A
ABCTB Investigators,
kConFab/AOCS Investigators,
Jager, A
Jakubowska, A
John, EM
Johnson, N
Jones, ME
Jung, A
Kaaks, R
Keeman, R
Khusnutdinova, E
Kitahara, CM
Ko, Y-D
Kosma, V-M
Koutros, S
Kraft, P
Kristensen, VN
Kubelka-Sabit, K
Kurian, AW
Lacey, JV
Lambrechts, D
Larson, NL
Linet, M
Ogrodniczak, A
Mannermaa, A
Manoukian, S
Margolin, S
Mavroudis, D
Milne, RL
Muranen, TA
Murphy, RA
Nevanlinna, H
Olson, JE
Olsson, H
Park-Simon, T-W
Perou, CM
Peterlongo, P
Plaseska-Karanfilska, D
Pylkäs, K
Rennert, G
Saloustros, E
Sandler, DP
Sawyer, EJ
Schmidt, MK
Schmutzler, RK
Shibli, R
Smeets, A
Soucy, P
Southey, MC
Swerdlow, AJ
Tamimi, RM
Taylor, JA
Teras, LR
Terry, MB
Tomlinson, I
Troester, MA
Truong, T
Vachon, CM
Wendt, C
Winqvist, R
Wolk, A
Yang, XR
Zheng, W
Ziogas, A
Simard, J
Dunning, AM
Pharoah, PDP
Easton, DF
Type
Journal Article
Metadata
Show full item recordAbstract
Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
Collections
Subject
NBCS Collaborators
CTS Consortium
ABCTB Investigators
kConFab/AOCS Investigators
Germ Cells
Humans
Breast Neoplasms
Risk Factors
Case-Control Studies
Genome, Human
Female
Genome-Wide Association Study
DNA Copy Number Variations
Research team
Functional Genetic Epidemiology
Aetiological Epidemiology
Language
eng
Date accepted
2021-12-01
License start date
2022-01-18
Citation
Communications biology, 2022, 5 (1), pp. 65 - ?
Publisher
NATURE PORTFOLIO