Journal Article

DKFZ-2023-01724

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk.

Wilcox, N. ; Dumont, M. ; González-Neira, A. ; Carvalho, S. ; Joly Beauparlant, C. ; Crotti, M. ; Luccarini, C. ; Soucy, P. ; Dubois, S. ; Nuñez-Torres, R. ; Pita, G. ; Gardner, E. J. ; Dennis, J. ; Alonso, M. R. ; Álvarez, N. ; Baynes, C. ; Collin-Deschesnes, A. C. ; Desjardins, S. ; Becher, H. ; Behrens, S.DKFZ* ; Bolla, M. K. ; Castelao, J. E. ; Chang-Claude, J.DKFZ* ; Cornelissen, S. ; Dörk, T. ; Engel, C. ; Gago-Dominguez, M. ; Guénel, P. ; Hadjisavvas, A. ; Hahnen, E. ; Hartman, M. ; Herráez, B. ; Investigators, S. (Collaboration Author) ; Jung, A. Y.DKFZ* ; Keeman, R. ; Kiechle, M. ; Li, J. ; Loizidou, M. A. ; Lush, M. ; Michailidou, K. ; Panayiotidis, M. I. ; Sim, X. ; Teo, S. H. ; Tyrer, J. P. ; van der Kolk, L. E. ; Wahlström, C. ; Wang, Q. ; Perry, J. R. B. ; Benitez, J. ; Schmidt, M. K. ; Schmutzler, R. K. ; Pharoah, P. D. P. ; Droit, A. ; Dunning, A. M. ; Kvist, A. ; Devilee, P. ; Easton, D. F. ; Simard, J. ; Tan, B. K. (Contributor) ; Tan, V. K. M. (Contributor) ; Tan, S.-M. (Contributor) ; Lim, G. H. (Contributor) ; Tan, E. Y. (Contributor) ; Ho, P. J. (Contributor) ; Khng, A. J. (Contributor)

2023
Macmillan Publishers Limited, part of Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s41588-023-01466-z

Abstract: Linkage and candidate gene studies have identified several breast cancer susceptibility genes, but the overall contribution of coding variation to breast cancer is unclear. To evaluate the role of rare coding variants more comprehensively, we performed a meta-analysis across three large whole-exome sequencing datasets, containing 26,368 female cases and 217,673 female controls. Burden tests were performed for protein-truncating and rare missense variants in 15,616 and 18,601 genes, respectively. Associations between protein-truncating variants and breast cancer were identified for the following six genes at exome-wide significance (P < 2.5 × 10-6): the five known susceptibility genes ATM, BRCA1, BRCA2, CHEK2 and PALB2, together with MAP3K1. Associations were also observed for LZTR1, ATR and BARD1 with P < 1 × 10-4. Associations between predicted deleterious rare missense or protein-truncating variants and breast cancer were additionally identified for CDKN2A at exome-wide significance. The overall contribution of coding variants in genes beyond the previously known genes is estimated to be small.

Note: 2023 Sep;55(9):1435-1439

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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