Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk

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...

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Detalles Bibliográficos
Autores: 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., Bolla, M.K., Castelao Fernández, José Esteban, Chang-Claude, J., Cornelissen, S., Dörk, T., Engel, C., Gago-Dominguez, M., Guénel, P., Hadjisavvas, A., Hahnen, E., Hartman, M., Herráez, B., Tan, B.K.-T., Tan, V.K.M., Tan, S.-M., Lim, G.H., Tan, E.Y., Ho, P.J., Khng, A.J., Jung, A., 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.
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/21467
Acceso en línea:https://portalcientifico.sergas.gal//documentos/64ec7b67e13d1f2d6d3b701e
http://hdl.handle.net/20.500.11940/21467
Access Level:acceso abierto
Palabra clave:Female
Humans
Exome Sequencing
Exome
Mutation, Missense
Neoplasms
AS Vigo
CHUVI
Descripción
Sumario: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.

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