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@ARTICLE{Dumont:164977,
author = {Dumont, Martine and Weber-Lassalle, Nana and
Joly-Beauparlant, Charles and Ernst, Corinna and Droit,
Arnaud and Feng, Bing-Jian and Dubois, Stéphane and
Collin-Deschesnes, Annie-Claude and Soucy, Penny and
Vallée, Maxime and Fournier, Frédéric and Lemaçon,
Audrey and Adank, Muriel A and Allen, Jamie and Altmüller,
Janine and Arnold, Norbert and Ausems, Margreet G E M and
Berutti, Riccardo and Bolla, Manjeet K and Bull, Shelley and
Carvalho, Sara and Cornelissen, Sten and Dufault, Michael R
and Dunning, Alison M and Engel, Christoph and Gehrig,
Andrea and Geurts-Giele, Willemina R R and Gieger, Christian
and Green, Jessica and Hackmann, Karl and Helmy, Mohamed and
Hentschel, Julia and Hogervorst, Frans B L and Hollestelle,
Antoinette and Hooning, Maartje J and Horváth, Judit and
Ikram, M Arfan and Kaulfuß, Silke and Keeman, Renske and
Kuang, Da and Luccarini, Craig and Maier, Wolfgang and
Martens, John W M and Niederacher, Dieter and Nürnberg,
Peter and Ott, Claus-Eric and Peters, Annette and Pharoah,
Paul D P and Ramirez, Alfredo and Ramser, Juliane and
Riedel-Heller, Steffi and Schmidt, Gunnar and Shah, Mitul
and Scherer, Martin and Stäbler, Antje and Strom, Tim M and
Sutter, Christian and Thiele, Holger and van Asperen,
Christi J and van der Kolk, Lizet and van der Luijt, Rob B
and Volk, Alexander E and Wagner, Michael and Waisfisz,
Quinten and Wang, Qing and Wang-Gohrke, Shan and Weber,
Bernhard H F and Genome Of The Netherlands Project and Ghs
Study Group and Devilee, Peter and Tavtigian, Sean and
Bader, Gary D and Meindl, Alfons and Goldgar, David E and
Andrulis, Irene L and Schmutzler, Rita K and Easton, Douglas
F and Schmidt, Marjanka K and Hahnen, Eric and Simard,
Jacques},
title = {{U}ncovering the {C}ontribution of {M}oderate-{P}enetrance
{S}usceptibility {G}enes to {B}reast {C}ancer by
{W}hole-{E}xome {S}equencing and {T}argeted {E}nrichment
{S}equencing of {C}andidate {G}enes in {W}omen of {E}uropean
{A}ncestry.},
journal = {Cancers},
volume = {14},
number = {14},
issn = {2072-6694},
address = {Basel},
publisher = {MDPI},
reportid = {DZNE-2022-01381},
pages = {3363},
year = {2022},
note = {CC BY},
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 ATM, CHEK2, and PALB2, 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 (Other) / genetic susceptibility (Other) /
moderate-penetrance genes (Other) / whole-exome sequencing
(Other)},
cin = {AG Klockgether},
ddc = {610},
cid = {I:(DE-2719)1011001},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35884425},
pmc = {pmc:PMC9317824},
doi = {10.3390/cancers14143363},
url = {https://pub.dzne.de/record/164977},
}