Rxivist logo

Rare copy number variants (CNVs) and breast cancer risk

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

Posted 21 May 2021
bioRxiv DOI: 10.1101/2021.05.20.444828

Background: 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. Results: 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. Conclusions: 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.

Download data

  • Downloaded 187 times
  • Download rankings, all-time:
    • Site-wide: 136,402
    • In genetics: 5,481
  • Year to date:
    • Site-wide: 48,374
  • Since beginning of last month:
    • Site-wide: 39,544

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

News