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dc.contributor.authorEsteves, F
dc.contributor.authorXavier, JM
dc.contributor.authorFord, AM
dc.contributor.authorRocha, C
dc.contributor.authorPharoah, PDP
dc.contributor.authorCaldas, C
dc.contributor.authorChin, S-F
dc.contributor.authorMaia, A-T
dc.coverage.spatialEngland
dc.date.accessioned2022-07-12T13:04:04Z
dc.date.available2022-07-12T13:04:04Z
dc.date.issued2022-06-27
dc.identifierS0959-8049(22)00322-7
dc.identifier.citationEuropean Journal of Cancer, 2022, 172 pp. 146 - 157en_US
dc.identifier.issn0959-8049
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5205
dc.identifier.eissn1879-0852
dc.identifier.eissn1879-0852
dc.identifier.doi10.1016/j.ejca.2022.05.034
dc.identifier.doi10.1016/j.ejca.2022.05.034
dc.description.abstractINTRODUCTION: Translation of genome-wide association study (GWAS) findings into preventive approaches is challenged by the identification of the causal risk variants and the understanding of the biological mechanisms by which they act. We present using allelic expression (AE) ratios to perform quantitative case-control analysis as a novel approach to identify risk associations, causal regulatory variants, and target genes. METHODS: Using the breast cancer (BC) risk locus 17q22 to validate this approach, we measured AE ratios in normal breast tissue samples from controls and cases, as well as from unmatched blood samples. Then we used in-silico and in-vitro analysis to map and functionally characterised candidate causal variants. RESULTS: We found a significant shift in the AE patterns of STXBP4 (rs2628315) and COX11 (rs17817901) in the normal breast tissue of cases and healthy controls. Preferential expression of the G-rs2628315 and A-rs17817901 alleles, more often observed in cases, was associated with an increased risk for BC. Analysis of blood samples from cases and controls found a similar association. Furthermore, we identified two putative cis-regulatory variants - rs17817901 and rs8066588 - that affect a miRNA and a transcription factor binding site, respectively. CONCLUSION: We propose causal variants and target genes for the 17q22 BC risk locus and show that using AE ratios in case-control association studies is helpful in identifying risk and mapping causal variants.
dc.formatPrint-Electronic
dc.format.extent146 - 157
dc.languageeng
dc.language.isoengen_US
dc.publisherElsevier BVen_US
dc.relation.ispartofEuropean Journal of Cancer
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAllelic expression
dc.subjectBreast cancer
dc.subjectCis-acting variants
dc.subjectExpression regulation
dc.subjectFunctional genomics
dc.subjectGenetic risk
dc.titleGermline allelic expression of genes at 17q22 locus associates with risk of breast cancer.en_US
dc.typeJournal Article
dcterms.dateAccepted2022-05-20
dc.date.updated2022-07-12T09:01:05Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1016/j.ejca.2022.05.034en_US
rioxxterms.licenseref.startdate2022-06-27
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/35772352
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.publication-statusPublished online
pubs.volume172
icr.researchteamBiol Childhood Leukaemiaen_US
dc.contributor.icrauthorFord, Anthony
icr.provenanceDeposited by Dr Tony Ford on 2022-07-12. Deposit type is initial. No. of files: 1. Files: Esteves F et al.pdf


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