Rare germline copy number variants (CNVs) and breast cancer risk.
Authors
Bolla, Manjeet K
Ahearn, Thomas U
Anton-Culver, Hoda
Antonenkova, Natalia N
Freeman, Laura E Beane
Beckmann, Matthias W
Benitez, Javier
Bermisheva, Marina
Bogdanova, Natalia V
Bojesen, Stig E
Brenner, Hermann
Castelao, Jose E
Chang-Claude, Jenny
Chenevix-Trench, Georgia
Clarke, Christine L
NBCS Collaborators
Collée, J Margriet
CTS Consortium
Couch, Fergus J
Cox, Angela
Cross, Simon S
Czene, Kamila
Devilee, Peter
Eliassen, A Heather
Eriksson, Mikael
Evans, D Gareth
Fasching, Peter A
Fletcher, Olivia
Flyger, Henrik
Gabrielson, Marike
Gago-Dominguez, Manuela
García-Closas, Montserrat
González-Neira, Anna
Guénel, Pascal
Hahnen, Eric
Haiman, Christopher A
Hall, Per
Hoppe, Reiner
Hopper, John L
Howell, Anthony
ABCTB Investigators
kConFab/AOCS Investigators
Jager, Agnes
John, Esther M
Jung, Audrey
Kaaks, Rudolf
Khusnutdinova, Elza
Kitahara, Cari M
Ko, Yon-Dschun
Kosma, Veli-Matti
Koutros, Stella
Kraft, Peter
Kubelka-Sabit, Katerina
Kurian, Allison W
Lacey, James V
Lambrechts, Diether
Linet, Martha
Ogrodniczak, Alicja
Mannermaa, Arto
Manoukian, Siranoush
Margolin, Sara
Mavroudis, Dimitrios
Muranen, Taru A
Murphy, Rachel A
Olsson, Håkan
Park-Simon, Tjoung-Won
Perou, Charles M
Saloustros, Emmanouil
Sandler, Dale P
Sawyer, Elinor J
Schmidt, Marjanka K
Schmutzler, Rita K
Shibli, Rana
Smeets, Ann
Soucy, Penny
Southey, Melissa C
Swerdlow, Anthony J
Tamimi, Rulla M
Taylor, Jack A
Teras, Lauren R
Terry, Mary Beth
Troester, Melissa A
Wendt, Camilla
Winqvist, Robert
Yang, Xiaohong R
Zheng, Wei
Publication Date
2022-01-18Journal Title
Commun Biol
ISSN
2399-3642
Publisher
Springer Science and Business Media LLC
Volume
5
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Dennis, J., Tyrer, J., Walker, L. C., Michailidou, K., Wilson, L., Bolla, M. K., Wang, J., et al. (2022). Rare germline copy number variants (CNVs) and breast cancer risk.. Commun Biol, 5 (1) https://doi.org/10.1038/s42003-021-02990-6
Abstract
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.
Keywords
Article, /631/67/1347, /631/208/205/2138, /45/43, article
Sponsorship
Cancer Research UK (CRUK-A16563)
Medical Research Council (G1000143)
National Cancer Institute (U19CA148537)
National Cancer Institute (R01CA128978)
National Cancer Institute (U19CA148065)
Cancer Research UK (CRUK-A10710)
Cancer Research UK (CRUK-A12014)
Cancer Research UK (CRUK-A10118)
Identifiers
s42003-021-02990-6, 2990
External DOI: https://doi.org/10.1038/s42003-021-02990-6
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333150
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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