Transcriptome-wide association study of breast cancer risk by estrogen-receptor status
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BiBTeXPrevious transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.
DOI: 10.1002/gepi.22288
Projects: GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer
Publication type: Journal article
Journal: Genetic epidemiology
Human Diseases: Breast cancer
Citation: Genet. Epidemiol. 44(5):442-468
Date Published: 1st Jul 2020
Registered Mode: imported from a bibtex file
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Created: 15th Jul 2020 at 13:31
Last updated: 7th Dec 2021 at 17:58
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The German Consortium for Hereditary Breast and Ovarian Cancer HBOC has been founded in 1996 by the German Cancer Aid and has been funded by the German Cancer Aid until recently. GC-HBOC currently comprises 17 university centers providing genetic counseling, histopathological and molecular tissue analysis, genetic testing, and specific structured surveillance programs for early cancer detection at each clinical unit, all based on defined standard operating procedures.
Programme: LIFE Management Cluster
Public web page: http://www.konsortium-familiaerer-brustkrebs.de/
Start date: 1st Jan 1996
Projects: LIFE Adult, LIFE - Leipzig Research Center for Civilization Diseases, GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer, GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer
Institutions: Institute for Medical Informatics, Statistics and Epidemiology (IMISE)
https://orcid.org/0000-0002-7247-282X
Projects: LHA - Leipzig Health Atlas, LIFE Adult, LIFE - Leipzig Research Center for Civilization Diseases, LIFE HNC - Head and Neck Cancer Group, LIFE Heart, MMML - Molecular mechanisms in malignant lymphoma, GLA - German Lymphoma Alliance, MMML Demonstrators - Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine, HaematoOpt - Individualized model-based managing of the next-cycle thrombopenia of CHOEP/CHOP treated patients based on platelets dynamics during the previous cycles, e:Med, GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer, GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer, MMML-MYC-SYS, NLP4CR - Natural Language Processing for Clinical Research, Genetical Statistics and Systems Biology, SepNet - German Competence Network Sepsis, LIFE Child, HNPCC-Sys - Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome, GGN - German Glioma Network, CAPSys - Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome, CapSys - Systems Medicine of Community Acquired Pneumonia, ProstataCA, HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia, SMITH - Smart Medical Information Technology for Healthcare, Task Force COVID-19 Leipzig, NFDI4Health, POLAR - Polypharmacy, Drug Interactions, Risks, Management of health information systems, LivSys Transfer - Transfer of the LivSys in vitro system for hepatotoxicity into application, Project Test Demonstrator, Fundus photography as tool for analysis of eyes of subjects with diabetes, Clinical Trials Leipzig, NFDI4Health - TA3 Services, STOP-NUC, SCALE-TORT, EarlyAMDRate
Institutions: Institute for Medical Informatics, Statistics and Epidemiology (IMISE)
https://orcid.org/0000-0001-8344-0658
Projects: LIFE Heart, LIFE - Leipzig Research Center for Civilization Diseases, LIFE HNC - Head and Neck Cancer Group, SepNet - German Competence Network Sepsis, GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer, LIFE Child, GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer, LIFE Adult
Web page: https://www.uniklinikum-leipzig.de/einrichtungen/life
Taxonomy URI: http://purl.obolibrary.org/obo/DOID_1612
Synonyms: breast tumor, mammary cancer, mammary tumor, malignant tumor of the breast, mammary neoplasm, primary breast cancer, malignant neoplasm of breast
Definitions: Xref MGI. OMIM mapping confirmed by DO. [SN]., A thoracic cancer that originates in the mammary gland.
