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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.
Ferreira, Manuel A; Gamazon, Eric R; Al-Ejeh, Fares; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Arason, Adalgeir; Arndt, Volker; Aronson, Kristan J; Arun, Banu K; Asseryanis, Ella; Azzollini, Jacopo; Balmaña, Judith; Barnes, Daniel R; Barrowdale, Daniel; Beckmann, Matthias W; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bialkowska, Katarzyna; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Borg, Ake; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Burwinkel, Barbara; Caldés, Trinidad; Caligo, Maria A; Campa, Daniele; Campbell, Ian; Canzian, Federico; Carter, Jonathan; Carter, Brian D; Castelao, Jose E; Chang-Claude, Jenny; Chanock, Stephen J; Christiansen, Hans; Chung, Wendy K; Claes, Kathleen B M; Clarke, Christine L; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Daly, Mary B; de la Hoya, Miguel; Dennis, Joe.
Afiliação
  • Ferreira MA; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia. Manuel.Ferreira@qimr.edu.au.
  • Gamazon ER; Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, 37235, USA.
  • Al-Ejeh F; Clare Hall, University of Cambridge, Cambridge, CB3 9AL, UK.
  • Aittomäki K; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Andrulis IL; Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, 00290, Helsinki, Finland.
  • Anton-Culver H; Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
  • Arason A; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
  • Arndt V; Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA, 92617.
  • Aronson KJ; Department of Pathology, Landspitali University Hospital, 101, Reykjavik, Iceland.
  • Arun BK; BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, 101, Reykjavik, Iceland.
  • Asseryanis E; Division of Clinical Epidemiology and Aging Research, C070, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
  • Azzollini J; Department of Public Health Sciences, and Cancer Research Institute, Queen's University, Kingston, ON, K7L 3N6, Canada.
  • Balmaña J; Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Barnes DR; Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, 1090, Vienna, Austria.
  • Barrowdale D; Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), 20133, Milan, Italy.
  • Beckmann MW; Oncogenetics Group, Vall dHebron Institute of Oncology (VHIO), 8035, Barcelona, Spain.
  • Behrens S; Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), University Hospital, Vall d'Hebron, 08035, Barcelona, Spain.
  • Benitez J; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
  • Bermisheva M; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
  • Bialkowska K; Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, 91054, Erlangen, Germany.
  • Blomqvist C; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
  • Bogdanova NV; Centro de Investigación en Red de Enfermedades Raras (CIBERER), 46010, Valencia, Spain.
  • Bojesen SE; Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), 28029, Madrid, Spain.
  • Bolla MK; Institute of Biochemistry and Genetics, Ufa Federal Research Centre of Russian Academy of Sciences, 450054, Ufa, Russia.
  • Borg A; Department of Genetics and Pathology, Pomeranian Medical University, 71-252, Szczecin, Poland.
  • Brauch H; Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, 00290, Finland.
  • Brenner H; Department of Oncology, Örebro University Hospital, 70185, Örebro, Sweden.
  • Broeks A; Department of Radiation Oncology, Hannover Medical School, 30625, Hannover, Germany.
  • Burwinkel B; Gynaecology Research Unit, Hannover Medical School, 30625, Hannover, Germany.
  • Caldés T; N.N. Alexandrov Research Institute of Oncology and Medical Radiology, 223040, Minsk, Belarus.
  • Caligo MA; Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730, Herlev, Denmark.
  • Campa D; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730, Herlev, Denmark.
  • Campbell I; Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
  • Canzian F; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
  • Carter J; Department of Oncology, Lund University and Skåne University Hospital, 222 41, Lund, Sweden.
  • Carter BD; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376, Stuttgart, Germany.
  • Castelao JE; University of Tübingen, 72074, Tübingen, Germany.
  • Chang-Claude J; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
  • Chanock SJ; Division of Clinical Epidemiology and Aging Research, C070, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
  • Christiansen H; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
  • Chung WK; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120, Heidelberg, Germany.
  • Claes KBM; Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 CX, Amsterdam, The Netherlands.
  • Clarke CL; Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
  • Couch FJ; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
  • Cox A; Department of Biology, University of Pisa, 56126, Pisa, Italy.
  • Cross SS; Research Department, Peter MacCallum Cancer Center, Melbourne, VIC, 3000, Australia.
  • Czene K; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, 3000, Australia.
  • Daly MB; Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
  • de la Hoya M; Department of Gynaecological Oncology, Chris O'Brien Lifehouse and The University of Sydney, Camperdown, NSW, 2050, Australia.
  • Dennis J; Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA, 30303.
Nat Commun ; 10(1): 1741, 2019 04 15.
Article em En | MEDLINE | ID: mdl-30988301
ABSTRACT
Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Predisposição Genética para Doença Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Austrália
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Predisposição Genética para Doença Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Austrália