TY  - JOUR
AU  - Wilcox, Naomi
AU  - Dumont, Martine
AU  - González-Neira, Anna
AU  - Carvalho, Sara
AU  - Joly Beauparlant, Charles
AU  - Crotti, Marco
AU  - Luccarini, Craig
AU  - Soucy, Penny
AU  - Dubois, Stéphane
AU  - Nuñez-Torres, Rocio
AU  - Pita, Guillermo
AU  - Gardner, Eugene J
AU  - Dennis, Joe
AU  - Alonso, M Rosario
AU  - Álvarez, Nuria
AU  - Baynes, Caroline
AU  - Collin-Deschesnes, Annie Claude
AU  - Desjardins, Sylvie
AU  - Becher, Heiko
AU  - Behrens, Sabine
AU  - Bolla, Manjeet K
AU  - Castelao, Jose E
AU  - Chang-Claude, Jenny
AU  - Cornelissen, Sten
AU  - Dörk, Thilo
AU  - Engel, Christoph
AU  - Gago-Dominguez, Manuela
AU  - Guénel, Pascal
AU  - Hadjisavvas, Andreas
AU  - Hahnen, Eric
AU  - Hartman, Mikael
AU  - Herráez, Belén
AU  - Jung, Audrey Ying-Chee
AU  - Keeman, Renske
AU  - Kiechle, Marion
AU  - Li, Jingmei
AU  - Loizidou, Maria A
AU  - Lush, Michael
AU  - Michailidou, Kyriaki
AU  - Panayiotidis, Mihalis I
AU  - Sim, Xueling
AU  - Teo, Soo Hwang
AU  - Tyrer, Jonathan P
AU  - van der Kolk, Lizet E
AU  - Wahlström, Cecilia
AU  - Wang, Qin
AU  - Perry, John R B
AU  - Benitez, Javier
AU  - Schmidt, Marjanka K
AU  - Schmutzler, Rita K
AU  - Pharoah, Paul D P
AU  - Droit, Arnaud
AU  - Dunning, Alison M
AU  - Kvist, Anders
AU  - Devilee, Peter
AU  - Easton, Douglas F
AU  - Simard, Jacques
TI  - Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk.
JO  - Nature genetics
VL  - 55
IS  - 9
SN  - 1061-4036
CY  - London
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - DKFZ-2023-01724
SP  - 1435-1439
PY  - 2023
N1  - 2023 Sep;55(9):1435-1439
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:37592023
DO  - DOI:10.1038/s41588-023-01466-z
UR  - https://inrepo02.dkfz.de/record/282340
ER  -