Rare germline copy number variants (CNVs) and breast cancer risk.

Dennis, Joe and Tyrer, Jonathan P and Walker, Logan C and Michailidou, Kyriaki and Dorling, Leila and Bolla, Manjeet K and Wang, Qin and Ahearn, Thomas U and Andrulis, Irene L and Anton-Culver, Hoda and Antonenkova, Natalia N and Arndt, Volker and Aronson, Kristan J and Freeman, Laura E Beane and Beckmann, Matthias W and Behrens, Sabine and Benitez, Javier and Bermisheva, Marina and Bogdanova, Natalia V and Bojesen, Stig E and Brenner, Hermann and Castelao, Jose E and Chang-Claude, Jenny and Chenevix-Trench, Georgia and Clarke, Christine L and Collée, J Margriet and Couch, Fergus J and Cox, Angela and Cross, Simon S and Czene, Kamila and Devilee, Peter and Dörk, Thilo and Dossus, Laure and Eliassen, A Heather and Eriksson, Mikael and Evans, D Gareth and Fasching, Peter A and Figueroa, Jonine and Fletcher, Olivia and Flyger, Henrik and Fritschi, Lin and Gabrielson, Marike and Gago-Dominguez, Manuela and García-Closas, Montserrat and Giles, Graham G and González-Neira, Anna and Guénel, Pascal and Hahnen, Eric and Haiman, Christopher A and Hall, Per and Hollestelle, Antoinette and Hoppe, Reiner and Hopper, John L and Howell, Anthony and Jager, Agnes and Jakubowska, Anna and John, Esther M and Johnson, Nichola and Jones, Michael E and Jung, Audrey and Kaaks, Rudolf and Keeman, Renske and Khusnutdinova, Elza and Kitahara, Cari M and Ko, Yon-Dschun and Kosma, Veli-Matti and Koutros, Stella and Kraft, Peter and Kristensen, Vessela N and Kubelka-Sabit, Katerina and Kurian, Allison W and Lacey, James V and Lambrechts, Diether and Larson, Nicole L and Linet, Martha and Ogrodniczak, Alicja and Mannermaa, Arto and Manoukian, Siranoush and Margolin, Sara and Mavroudis, Dimitrios and Milne, Roger L and Muranen, Taru A and Murphy, Rachel A and Nevanlinna, Heli and Olson, Janet E and Olsson, Håkan and Park-Simon, Tjoung-Won and Perou, Charles M and Peterlongo, Paolo and Plaseska-Karanfilska, Dijana and Pylkäs, Katri and Rennert, Gad and Saloustros, Emmanouil and Sandler, Dale P and Sawyer, Elinor J and Schmidt, Marjanka K and Schmutzler, Rita K and Shibli, Rana and Smeets, Ann and Soucy, Penny and Southey, Melissa C and Swerdlow, Anthony J and Tamimi, Rulla M and Taylor, Jack A and Teras, Lauren R and Terry, Mary Beth and Tomlinson, Ian and Troester, Melissa A and Truong, Thérèse and Vachon, Celine M and Wendt, Camilla and Winqvist, Robert and Wolk, Alicja and Yang, Xiaohong R and Zheng, Wei and Ziogas, Argyrios and Simard, Jacques and Dunning, Alison M and Pharoah, Paul D P and Easton, Douglas F (2022) Rare germline copy number variants (CNVs) and breast cancer risk. Communications biology, 5 (1). p. 65. ISSN 2399-3642

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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.

Item Type: Article
Impact Factor Value: 6.548
Subjects: Medical and Health Sciences > Basic medicine
Medical and Health Sciences > Clinical medicine
Medical and Health Sciences > Health sciences
Medical and Health Sciences > Other medical sciences
Divisions: Faculty of Medical Science
Depositing User: Katerina Kubelka-Sabit
Date Deposited: 13 Jan 2023 10:54
Last Modified: 13 Jan 2023 10:54
URI: https://eprints.ugd.edu.mk/id/eprint/30758

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