Germline allelic expression of genes at 17q22 locus associates with risk of breast cancer
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.1/18654 |
Resumo: | Introduction: 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 caseecontrol 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 caseecontrol association studies is helpful in identifying risk and mapping causal variants. |
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Germline allelic expression of genes at 17q22 locus associates with risk of breast cancerAllelic expressionBreast cancerGenetic riskCis-acting variantsIntroduction: 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 caseecontrol 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 caseecontrol association studies is helpful in identifying risk and mapping causal variants.ElsevierSapientiaEsteves, FilipaM Xavier, JoanaFord, Anthony M.Rocha, CátiaPharoah, Paul D. P.Caldas, CarlosChin, Suet-FeungMaia, Ana-Teresa2022-12-19T10:25:47Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/18654eng0959-804910.1016/j.ejca.2022.05.034info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:30:56Zoai:sapientia.ualg.pt:10400.1/18654Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:08:23.987115Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Germline allelic expression of genes at 17q22 locus associates with risk of breast cancer |
title |
Germline allelic expression of genes at 17q22 locus associates with risk of breast cancer |
spellingShingle |
Germline allelic expression of genes at 17q22 locus associates with risk of breast cancer Esteves, Filipa Allelic expression Breast cancer Genetic risk Cis-acting variants |
title_short |
Germline allelic expression of genes at 17q22 locus associates with risk of breast cancer |
title_full |
Germline allelic expression of genes at 17q22 locus associates with risk of breast cancer |
title_fullStr |
Germline allelic expression of genes at 17q22 locus associates with risk of breast cancer |
title_full_unstemmed |
Germline allelic expression of genes at 17q22 locus associates with risk of breast cancer |
title_sort |
Germline allelic expression of genes at 17q22 locus associates with risk of breast cancer |
author |
Esteves, Filipa |
author_facet |
Esteves, Filipa M Xavier, Joana Ford, Anthony M. Rocha, Cátia Pharoah, Paul D. P. Caldas, Carlos Chin, Suet-Feung Maia, Ana-Teresa |
author_role |
author |
author2 |
M Xavier, Joana Ford, Anthony M. Rocha, Cátia Pharoah, Paul D. P. Caldas, Carlos Chin, Suet-Feung Maia, Ana-Teresa |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Esteves, Filipa M Xavier, Joana Ford, Anthony M. Rocha, Cátia Pharoah, Paul D. P. Caldas, Carlos Chin, Suet-Feung Maia, Ana-Teresa |
dc.subject.por.fl_str_mv |
Allelic expression Breast cancer Genetic risk Cis-acting variants |
topic |
Allelic expression Breast cancer Genetic risk Cis-acting variants |
description |
Introduction: 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 caseecontrol 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 caseecontrol association studies is helpful in identifying risk and mapping causal variants. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-12-19T10:25:47Z 2022 2022-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.1/18654 |
url |
http://hdl.handle.net/10400.1/18654 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0959-8049 10.1016/j.ejca.2022.05.034 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799133330447269888 |