2024-03-29T13:10:51Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/74332023-10-05T07:38:52Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
Repisalud
author
Walker, Logan C
author
Marquart, Louise
author
Pearson, John F
author
Wiggins, George A R
author
O'Mara, Tracy A
author
Parsons, Michael T
author
Barrowdale, Daniel
author
McGuffog, Lesley
author
Dennis, Joe
author
Benitez, Javier
author
Slavin, Thomas P
author
Radice, Paolo
author
Frost, Debra
author
Godwin, Andrew K
author
Meindl, Alfons
author
Schmutzler, Rita Katharina
author
Isaacs, Claudine
author
Peshkin, Beth N
author
Caldes, Trinidad
author
Hogervorst, Frans Bl
author
Lazaro, Conxi
author
Jakubowska, Anna
author
Montagna, Marco
author
Chen, Xiaoqing
author
Offit, Kenneth
author
Hulick, Peter J
author
Andrulis, Irene L
author
Lindblom, Annika
author
Nussbaum, Robert L
author
Nathanson, Katherine L
author
Chenevix-Trench, Georgia
author
Antoniou, Antonis C
author
Couch, Fergus J
author
Spurdle, Amanda B
funder
National Science Foundation (Estados Unidos)
funder
Asociación Española Contra el Cáncer
funder
Fundación Mutua Madrileña
funder
Wellcome Trust
funder
University of Kansas. Cancer Center (Estados Unidos)
funder
Netherlands Comprehensive Cancer Organisation
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Dutch Research Council (Holanda)
funder
Cancer Council of South (Australia)
2019-04-03T11:26:59Z
2019-04-03T11:26:59Z
2017-04-25
Eur J Hum Genet. 2017;25(4):432-438
1018-4813
http://hdl.handle.net/20.500.12105/7433
28145423
10.1038/ejhg.2016.203
1476-5438
European journal of human genetics : EJHG
Genome-wide studies of patients carrying pathogenic variants (mutations) in BRCA1 or BRCA2 have reported strong associations between single-nucleotide polymorphisms (SNPs) and cancer risk. To conduct the first genome-wide association analysis of copy-number variants (CNVs) with breast or ovarian cancer risk in a cohort of 2500 BRCA1 pathogenic variant carriers, CNV discovery was performed using multiple calling algorithms and Illumina 610k SNP array data from a previously published genome-wide association study. Our analysis, which focused on functionally disruptive genomic deletions overlapping gene regions, identified a number of loci associated with risk of breast or ovarian cancer for BRCA1 pathogenic variant carriers. Despite only including putative deletions called by at least two or more algorithms, detection of selected CNVs by ancillary molecular technologies only confirmed 40% of predicted common (>1% allele frequency) variants. These include four loci that were associated (unadjusted P<0.05) with breast cancer (GTF2H2, ZNF385B, NAALADL2 and PSG5), and two loci associated with ovarian cancer (CYP2A7 and OR2A1). An interesting finding from this study was an association of a validated CNV deletion at the CYP2A7 locus (19q13.2) with decreased ovarian cancer risk (relative risk=0.50, P=0.007). Genomic analysis found this deletion coincides with a region displaying strong regulatory potential in ovarian tissue, but not in breast epithelial cells. This study highlighted the need to verify CNVs in vitro, but also provides evidence that experimentally validated CNVs (with plausible biological consequences) can modify risk of breast or ovarian cancer in BRCA1 pathogenic variant carriers.
eng
Evaluation of copy-number variants as modifiers of breast and ovarian cancer risk for BRCA1 pathogenic variant carriers
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/7433/1/Evaluationofcopy-numbervariants_2017.pdf
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https://repisalud.isciii.es/bitstream/20.500.12105/7433/3/Evaluationofcopy-numbervariants_2017.pdf.txt
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Evaluationofcopy-numbervariants_2017.pdf.txt