Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

被引：0

作者：

Manuel A. Ferreira

Eric R. Gamazon

Fares Al-Ejeh

Kristiina Aittomäki

Irene L. Andrulis

Hoda Anton-Culver

Adalgeir Arason

Volker Arndt

Kristan J. Aronson

Banu K. Arun

Ella Asseryanis

Jacopo Azzollini

Judith Balmaña

Daniel R. Barnes

Daniel Barrowdale

Matthias W. Beckmann

Sabine Behrens

Javier Benitez

Marina Bermisheva

Katarzyna Białkowska

Carl Blomqvist

Natalia V. Bogdanova

Stig E. Bojesen

Manjeet K. Bolla

Ake Borg

Hiltrud Brauch

Hermann Brenner

Annegien Broeks

Barbara Burwinkel

Trinidad Caldés

Maria A. Caligo

Daniele Campa

Ian Campbell

Federico Canzian

Jonathan Carter

Brian D. Carter

Jose E. Castelao

Jenny Chang-Claude

Stephen J. Chanock

Hans Christiansen

Wendy K. Chung

Kathleen B. M. Claes

Christine L. Clarke

Fergus J. Couch

Angela Cox

Simon S. Cross

Kamila Czene

Mary B. Daly

Miguel de la Hoya

Joe Dennis

机构：

[1] QIMR Berghofer Medical Research Institute,Department of Genetics and Computational Biology

[2] Vanderbilt University,Division of Genetic Medicine, Department of Medicine

[3] University of Cambridge,Clare Hall

[4] University of Helsinki,Department of Clinical Genetics, Helsinki University Hospital

[5] Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital,Fred A. Litwin Center for Cancer Genetics

[6] University of Toronto,Department of Molecular Genetics

[7] University of California Irvine,Department of Epidemiology, Genetic Epidemiology Research Institute

[8] Landspitali University Hospital,Department of Pathology

[9] University of Iceland,BMC (Biomedical Centre), Faculty of Medicine

[10] German Cancer Research Center (DKFZ),Division of Clinical Epidemiology and Aging Research, C070

[11] Queen’s University,Department of Public Health Sciences, and Cancer Research Institute

[12] University of Texas MD Anderson Cancer Center,Department of Breast Medical Oncology

[13] Medical University of Vienna,Dept of OB/GYN and Comprehensive Cancer Center

[14] Fondazione IRCCS Istituto Nazionale dei Tumori (INT),Unit of Medical Genetics, Department of Medical Oncology and Hematology

[15] Vall dHebron Institute of Oncology (VHIO),Oncogenetics Group

[16] University Hospital,Department of Medical Oncology, Vall d’Hebron Institute of Oncology (VHIO)

[17] University of Cambridge,Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care

[18] Friedrich-Alexander-University Erlangen-Nuremberg,Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER

[19] German Cancer Research Center (DKFZ),EMN, University Hospital Erlangen

[20] Centro de Investigación en Red de Enfermedades Raras (CIBERER),Division of Cancer Epidemiology

[21] Spanish National Cancer Research Centre (CNIO),Human Cancer Genetics Programme

[22] Ufa Federal Research Centre of Russian Academy of Sciences,Institute of Biochemistry and Genetics

[23] Pomeranian Medical University,Department of Genetics and Pathology

[24] University of Helsinki,Department of Oncology, Helsinki University Hospital

[25] Örebro University Hospital,Department of Oncology

[26] Hannover Medical School,Department of Radiation Oncology

[27] Hannover Medical School,Gynaecology Research Unit

[28] N.N. Alexandrov Research Institute of Oncology and Medical Radiology,Copenhagen General Population Study

[29] Herlev and Gentofte Hospital,Department of Clinical Biochemistry, Herlev and Gentofte Hospital

[30] Copenhagen University Hospital,Faculty of Health and Medical Sciences

[31] Copenhagen University Hospital,Department of Oncology

[32] University of Copenhagen,German Cancer Consortium (DKTK)

[33] Lund University and Skåne University Hospital,Division of Preventive Oncology

[34] Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology,Division of Molecular Pathology

[35] University of Tübingen,Molecular Epidemiology Group, C080

[36] German Cancer Research Center (DKFZ),Molecular Biology of Breast Cancer

[37] German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT),Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos

[38] The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital,Section of Molecular Genetics, Dept. of Laboratory Medicine

[39] German Cancer Research Center (DKFZ),Department of Biology

[40] University Womens Clinic Heidelberg,Research Department

[41] University of Heidelberg,Sir Peter MacCallum Department of Oncology

[42] IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos),Genomic Epidemiology Group

[43] University Hospital of Pisa,Department of Gynaecological Oncology

[44] University of Pisa,Behavioral and Epidemiology Research Group

[45] Peter MacCallum Cancer Center,Oncology and Genetics Unit

[46] The University of Melbourne,Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH)

[47] German Cancer Research Center (DKFZ),Departments of Pediatrics and Medicine

[48] Chris O’Brien Lifehouse and The University of Sydney,Centre for Medical Genetics

[49] American Cancer Society,Westmead Institute for Medical Research

[50] Instituto de Investigacion Sanitaria Galicia Sur (IISGS),Department of Laboratory Medicine and Pathology

来源：

Nature Communications | / 10卷

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摘要：

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.

引用

共 50 条

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Ferreira, Manuel A.
Gamazon, Eric R.
Al-Ejeh, Fares
Aittomaki, Kristiina
Andrulis, Irene L.
Anton-Culver, Hoda
Arason, Adalgeir
Arndt, Volker
Aronson, Kristan J.
Arun, Banu K.
Asseryanis, Ella
Azzollini, Jacopo
Balmana, 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
Caldes, 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
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[2] Genome-wide association studies identify four ER negative–specific breast cancer risk loci
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[J]. JOURNAL OF IMMUNOLOGY RESEARCH, 2022, 2022
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[8] A Comprehensive cis-eQTL Analysis Revealed Target Genes in Breast Cancer Susceptibility Loci Identified in Genome-wide Association Studies
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