Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

2.50
Hdl Handle:
http://hdl.handle.net/11287/617910
Title:
Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
Authors:
Vigorito, E. [et al]; Brewer, Carole
Abstract:
Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
Citation:
Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers., 11 (7):e0158801 PLoS ONE
Publisher:
PLoS One
Journal:
PloS one
Issue Date:
27-Jul-2016
URI:
http://hdl.handle.net/11287/617910
DOI:
10.1371/journal.pone.0158801
PubMed ID:
27463617
Additional Links:
http://journals.plos.org/plosone/article/authors?id=10.1371%2Fjournal.pone.0158801
Note:
This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
Clinical Genetics (Peninsula Genetics); 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorVigorito, E. [et al]en
dc.contributor.authorBrewer, Caroleen
dc.date.accessioned2016-08-04T09:23:40Z-
dc.date.available2016-08-04T09:23:40Z-
dc.date.issued2016-07-27-
dc.identifier.citationFine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers., 11 (7):e0158801 PLoS ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid27463617-
dc.identifier.doi10.1371/journal.pone.0158801-
dc.identifier.urihttp://hdl.handle.net/11287/617910-
dc.description.abstractPopulation-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.en
dc.languageENG-
dc.language.isoenen
dc.publisherPLoS Oneen
dc.relation.urlhttp://journals.plos.org/plosone/article/authors?id=10.1371%2Fjournal.pone.0158801en
dc.rightsArchived with thanks to PloS One. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.en
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleFine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.en
dc.typeJournal Articleen
dc.identifier.journalPloS oneen
dc.description.noteThis article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.en
dc.type.versionPublisheden

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