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

Authors :
Dennis, Joe
Tyrer, Jonathan P.
Walker, Logan C.
Michailidou, Kyriaki
Dorling, Leila
Bolla, Manjeet K.
Wang, Qin
Ahearn, Thomas U.
Andrulis, Irene L.
Anton-Culver, Hoda
Antonenkova, Natalia N.
Arndt, Volker
Aronson, Kristan J.
Freeman, Laura E. Beane
Beckmann, Matthias W.
Behrens, Sabine
Benitez, Javier
Bermisheva, Marina
Bogdanova, Natalia V.
Bojesen, Stig E.
Source :
Communications Biology; 1/18/2022, Vol. 5 Issue 1, p1-15, 15p
Publication Year :
2022

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. Dennis et al. investigate potential breast cancer associations with rare germline copy number variants (CNVs) by conducting a genome-wide analysis in a large breast cancer case-control dataset. The authors detected associations with exonic deletions in established breast cancer susceptibility genes and suggestive associations for a number of non-coding CNVs. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
23993642
Volume :
5
Issue :
1
Database :
Complementary Index
Journal :
Communications Biology
Publication Type :
Academic Journal
Accession number :
154738689
Full Text :
https://doi.org/10.1038/s42003-021-02990-6