Rare germline copy number variants (CNVs) and breast cancer risk
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Published:2022-01-18
Issue:1
Volume:5
Page:
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ISSN:2399-3642
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Container-title:Communications Biology
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language:en
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Short-container-title:Commun Biol
Author:
Dennis JoeORCID, Tyrer Jonathan P.ORCID, Walker Logan C.ORCID, Michailidou KyriakiORCID, Dorling Leila, Bolla Manjeet K., Wang QinORCID, Ahearn Thomas U., Andrulis Irene L.ORCID, Anton-Culver Hoda, Antonenkova Natalia N., Arndt VolkerORCID, Aronson Kristan J.ORCID, Freeman Laura E. Beane, Beckmann Matthias W., Behrens SabineORCID, Benitez Javier, Bermisheva Marina, Bogdanova Natalia V., Bojesen Stig E., Brenner Hermann, Castelao Jose E., Chang-Claude Jenny, Chenevix-Trench Georgia, Clarke Christine L., Kristensen Vessela N.ORCID, Sahlberg Kristine K., Børresen-Dale Anne-Lise, Gram Inger Torhild, Engebråten Olav, Naume Bjørn, Geisler Jürgen, Alnæs Grethe I. Grenaker, Collée J. Margriet, Lacey James, Martinez Elena, Couch Fergus J., Cox Angela, Cross Simon S., Czene Kamila, Devilee Peter, Dörk ThiloORCID, Dossus LaureORCID, Eliassen A. Heather, Eriksson Mikael, Evans D. Gareth, Fasching Peter A., Figueroa JonineORCID, Fletcher Olivia, Flyger Henrik, Fritschi LinORCID, Gabrielson Marike, Gago-Dominguez Manuela, García-Closas Montserrat, Giles Graham G.ORCID, González-Neira Anna, Guénel Pascal, Hahnen Eric, Haiman Christopher A., Hall Per, Hollestelle AntoinetteORCID, Hoppe Reiner, Hopper John L., Howell Anthony, Clarke Christine, Carpenter Jane, Marsh Deborah, Scott Rodney, Baxter Robert, Yip Desmond, Davis Alison, Pathmanathan Nirmala, Simpson Peter, Graham Dinny, Sachchithananthan Mythily, Campbell Ian, de Fazio Anna, Fox Stephen, Kirk Judy, Lindeman Geoff, Milne Roger, Southey Melissa, Spurdle Amanda, Thorne Heather, Jager Agnes, Jakubowska AnnaORCID, John Esther M., Johnson NicholaORCID, Jones Michael E.ORCID, Jung Audrey, Kaaks Rudolf, Keeman RenskeORCID, Khusnutdinova Elza, Kitahara Cari M., Ko Yon-Dschun, Kosma Veli-Matti, Koutros Stella, Kraft Peter, Kristensen Vessela N.ORCID, Kubelka-Sabit Katerina, Kurian Allison W., Lacey James V., Lambrechts Diether, Larson Nicole L.ORCID, Linet Martha, Ogrodniczak Alicja, Mannermaa Arto, Manoukian Siranoush, Margolin Sara, Mavroudis Dimitrios, Milne Roger L.ORCID, Muranen Taru A., Murphy Rachel A., Nevanlinna HeliORCID, Olson Janet E.ORCID, Olsson Håkan, Park-Simon Tjoung-Won, Perou Charles M., Peterlongo PaoloORCID, Plaseska-Karanfilska DijanaORCID, Pylkäs KatriORCID, Rennert GadORCID, 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, Tomlinson IanORCID, Troester Melissa A., Truong ThérèseORCID, Vachon Celine M.ORCID, Wendt Camilla, Winqvist Robert, Wolk AlicjaORCID, Yang Xiaohong R., Zheng Wei, Ziogas ArgyriosORCID, Simard JacquesORCID, Dunning Alison M.ORCID, Pharoah Paul D. P.ORCID, Easton Douglas F.ORCID, , , ,
Abstract
AbstractGermline 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.
Funder
Cancer Research UK
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference36 articles.
1. Abel, H.J. et al. Mapping and characterization of structural variation in 17,795 human genomes. Nature 583, 83–89 (2020). 2. Collins, R. L. et al. A structural variation reference for medical and population genetics. Nature. 581, 444–451 (2020). 3. Sudmant, P.H. et al. An integrated map of structural variation in 2,504 human genomes. Nature 526, 75−81 (2015). 4. Nik-Zainal, S. et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534, 47–54 (2016). 5. Gerstung, M. et al. The evolutionary history of 2,658 cancers. Nature 578, 122–128 (2020).
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