Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Uncovering the contribution of moderate-penetrance susceptibility genes to breast cancer by whole-exome sequencing and targeted enrichment sequencing of candidate genes in women of European ancestry

[img]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
990kB
[img] Other (Supplementary Materials)
2MB

Item Type:Article
Title:Uncovering the contribution of moderate-penetrance susceptibility genes to breast cancer by whole-exome sequencing and targeted enrichment sequencing of candidate genes in women of European ancestry
Creators Name:Dumont, M. and Weber-Lassalle, N. and Joly-Beauparlant, C. and Ernst, C. and Droit, A. and Feng, B.J. and Dubois, S. and Collin-Deschesnes, A.C. and Soucy, P. and Vallée, M. and Fournier, F. and Lemaçon, A. and Adank, M.A. and Allen, J. and Altmüller, J. and Arnold, N. and Ausems, M.G.E.M. and Berutti, R. and Bolla, M.K. and Bull, S. and Carvalho, S. and Cornelissen, S. and Dufault, M.R. and Dunning, A.M. and Engel, C. and Gehrig, A. and Geurts-Giele, W.R.R. and Gieger, C. and Green, J. and Hackmann, K. and Helmy, M. and Hentschel, J. and Hogervorst, F.B.L. and Hollestelle, A. and Hooning, M.J. and Horváth, J. and Ikram, M.A. and Kaulfuß, S. and Keeman, R. and Kuang, D. and Luccarini, C. and Maier, W. and Martens, J.W.M. and Niederacher, D. and Nürnberg, P. and Ott, C.E. and Peters, A. and Pharoah, P.D.P. and Ramirez, A. and Ramser, J. and Riedel-Heller, S. and Schmidt, G. and Shah, M. and Scherer, M. and Stäbler, A. and Strom, T.M. and Sutter, C. and Thiele, H. and van Asperen, C.J. and van der Kolk, L. and van der Luijt, R.B. and Volk, A.E. and Wagner, M. and Waisfisz, Q. and Wang, Q. and Wang-Gohrke, S. and Weber, B.H.F. and Devilee, P. and Tavtigian, S. and Bader, G.D. and Meindl, A. and Goldgar, D.E. and Andrulis, I.L. and Schmutzler, R.K. and Easton, D.F. and Schmidt, M.K. and Hahnen, E. and Simard, J.
Abstract:Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to , and , however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes.
Keywords:Breast Cancer, Genetic Susceptibility, Whole-Exome Sequencing, Moderate-Penetrance Genes
Source:Cancers
ISSN:2072-6694
Publisher:MDPI
Volume:14
Number:14
Page Range:3363
Date:11 July 2022
Official Publication:https://doi.org/10.3390/cancers14143363
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library