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http://hdl.handle.net/2445/171642
Title: | Evaluation of copy-number variants as modifiers of breast and ovarian cancer risk for BRCA1 pathogenic variant carriers |
Author: | Lázaro García, Conxi BCFR Investigators EMBRACE Collaborators GEMO Study Collaborators HEBON Investigators KConFab Investigators |
Keywords: | Càncer de mama Càncer d'ovari Etiologia Breast cancer Ovarian cancer Etiology |
Issue Date: | 1-Feb-2017 |
Publisher: | Nature Publishing Group |
Abstract: | 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 (41% allele frequency) variants. These include four loci that were associated (unadjusted Po0.05) 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/ejhg.2016.203 |
It is part of: | European Journal of Human Genetics, 2017, vol. 25, p. 432-438 |
URI: | http://hdl.handle.net/2445/171642 |
Related resource: | https://doi.org/10.1038/ejhg.2016.203 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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WalkerLC.pdf | 401.28 kB | Adobe PDF | View/Open | |
WalkerLC_cor.pdf | Correction | 224.27 kB | Adobe PDF | View/Open |
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