IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-05427-7.html
   My bibliography  Save this article

Identification of nine new susceptibility loci for endometrial cancer

Author

Listed:
  • Tracy A. O’Mara

    (QIMR Berghofer Medical Research Institute)

  • Dylan M. Glubb

    (QIMR Berghofer Medical Research Institute)

  • Frederic Amant

    (University Hospitals KU Leuven, University of Leuven, Division of Gynecologic Oncology)

  • Daniela Annibali

    (University Hospitals KU Leuven, University of Leuven, Division of Gynecologic Oncology)

  • Katie Ashton

    (John Hunter Hospital, Hunter Medical Research Institute
    University of Newcastle, Centre for Information Based Medicine
    University of Newcastle, Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health)

  • John Attia

    (John Hunter Hospital, Hunter Medical Research Institute
    University of Newcastle, Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health)

  • Paul L. Auer

    (Fred Hutchinson Cancer Research Center
    University of Wisconsin-Milwaukee, Zilber School of Public Health)

  • Matthias W. Beckmann

    (University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center ER-EMN)

  • Amanda Black

    (National Cancer Institute, Division of Cancer Epidemiology and Genetics)

  • Manjeet K. Bolla

    (University of Cambridge, Centre for Cancer Genetic Epidemiology)

  • Hiltrud Brauch

    (Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
    University of Tübingen
    German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK))

  • Hermann Brenner

    (German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ)
    German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT))

  • Louise Brinton

    (National Cancer Institute, Division of Cancer Epidemiology and Genetics)

  • Daniel D. Buchanan

    (The University of Melbourne
    The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health
    Royal Melbourne Hospital
    University of Melbourne Centre for Cancer Research)

  • Barbara Burwinkel

    (University of Heidelberg
    German Cancer Research Center (DKFZ))

  • Jenny Chang-Claude

    (German Cancer Research Center (DKFZ)
    University Medical Center Hamburg-Eppendorf, Cancer Epidemiology, University Cancer Center Hamburg (UCCH))

  • Stephen J. Chanock

    (National Cancer Institute, Division of Cancer Epidemiology and Genetics)

  • Chu Chen

    (Fred Hutchinson Cancer Research Center)

  • Maxine M. Chen

    (Harvard T.H. Chan School of Public Health)

  • Timothy H. T. Cheng

    (University of Oxford, Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre)

  • Christine L. Clarke

    (University of Sydney, Westmead Institute for Medical Research)

  • Mark Clendenning

    (The University of Melbourne
    University of Melbourne Centre for Cancer Research)

  • Linda S. Cook

    (University of New Mexico, University of New Mexico Health Sciences Center
    Alberta Health Services)

  • Fergus J. Couch

    (Mayo Clinic)

  • Angela Cox

    (University of Sheffield, Sheffield Institute for Nucleic Acids (SInFoNiA))

  • Marta Crous-Bous

    (Harvard T.H. Chan School of Public Health
    Harvard Medical School, Channing Division of Network Medicine, Brigham and Women’s Hospital)

  • Kamila Czene

    (Karolinska Institutet)

  • Felix Day

    (University of Cambridge, MRC Epidemiology Unit, School of Clinical Medicine)

  • Joe Dennis

    (University of Cambridge, Centre for Cancer Genetic Epidemiology)

  • Jeroen Depreeuw

    (University Hospitals KU Leuven, University of Leuven, Division of Gynecologic Oncology
    VIB, Vesalius Research Center
    University of Leuven, Laboratory for Translational Genetics)

  • Jennifer Anne Doherty

    (University of Utah)

  • Thilo Dörk

    (Hannover Medical School)

  • Sean C. Dowdy

    (Mayo Clinic, Division of Gynecologic Oncology)

  • Matthias Dürst

    (Jena University Hospital - Friedrich Schiller University)

  • Arif B. Ekici

    (Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Institute of Human Genetics, University Hospital Erlangen)

  • Peter A. Fasching

    (University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center ER-EMN
    University of California at Los Angeles, David Geffen School of Medicine, Division of Hematology and Oncology)

  • Brooke L. Fridley

    (Kansas University Medical Center)

  • Christine M. Friedenreich

    (Alberta Health Services)

  • Lin Fritschi

    (Curtin University, School of Public Health)

  • Jenny Fung

    (University of Queensland, Institute for Molecular Bioscience)

  • Montserrat García-Closas

    (National Cancer Institute, Division of Cancer Epidemiology and Genetics
    Division of Genetics and Epidemiology)

  • Mia M. Gaudet

    (Epidemiology Research Program)

  • Graham G. Giles

    (The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health
    Cancer Council Victoria
    Monash University)

  • Ellen L. Goode

    (Mayo Clinic, Division of Epidemiology)

  • Maggie Gorman

    (University of Oxford, Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre)

  • Christopher A. Haiman

    (University of Southern California, Keck School of Medicine)

  • Per Hall

    (Karolinska Institutet
    South General Hospital)

  • Susan E. Hankison

    (Harvard Medical School, Channing Division of Network Medicine, Brigham and Women’s Hospital
    University of Massachusetts, Amherst)

  • Catherine S. Healey

    (University of Cambridge, Centre for Cancer Genetic Epidemiology)

  • Alexander Hein

    (University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center ER-EMN)

  • Peter Hillemanns

    (Hannover Medical School)

  • Shirley Hodgson

    (St George’s, University of London)

  • Erling A. Hoivik

    (University of Bergen, Centre for Cancer Biomarkers
    Haukeland University Hospital)

  • Elizabeth G. Holliday

    (John Hunter Hospital, Hunter Medical Research Institute
    University of Newcastle, Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health)

  • John L. Hopper

    (The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health)

  • David J. Hunter

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health)

  • Angela Jones

    (University of Oxford, Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre)

  • Camilla Krakstad

    (University of Bergen, Centre for Cancer Biomarkers
    Haukeland University Hospital)

  • Vessela N. Kristensen

    (Oslo University Hospital, Radiumhospitalet, Institute for Cancer Research
    University of Oslo, Institute of Clinical Medicine, Faculty of Medicine
    University of Oslo, Oslo University Hospital)

  • Diether Lambrechts

    (University of Leuven, Laboratory for Translational Genetics
    VIB, VIB Center for Cancer Biology)

  • Loic Le Marchand

    (University of Hawaii Cancer Center)

  • Xiaolin Liang

    (Memorial Sloan-Kettering Cancer Center)

  • Annika Lindblom

    (Karolinska Institutet)

  • Jolanta Lissowska

    (M. Sklodowska-Curie Cancer Center-Oncology Institute)

  • Jirong Long

    (Vanderbilt University School of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center)

  • Lingeng Lu

    (Yale School of Public Health)

  • Anthony M. Magliocco

    (Moffitt Cancer Center and Research Institute)

  • Lynn Martin

    (University of Birmingham, Institute of Cancer and Genomic Sciences)

  • Mark McEvoy

    (University of Newcastle, Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health)

  • Alfons Meindl

    (Ludwig-Maximilians University of Munich)

  • Kyriaki Michailidou

    (University of Cambridge, Centre for Cancer Genetic Epidemiology
    The Cyprus Institute of Neurology and Genetics)

  • Roger L. Milne

    (The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health
    Cancer Council Victoria)

  • Miriam Mints

    (Karolinska Institutet)

  • Grant W. Montgomery

    (QIMR Berghofer Medical Research Institute
    University of Queensland, Institute for Molecular Bioscience)

  • Rami Nassir

    (University of California Davis)

  • Håkan Olsson

    (Lund University)

  • Irene Orlow

    (Memorial Sloan-Kettering Cancer Center)

  • Geoffrey Otton

    (University of Newcastle, School of Medicine and Public Health)

  • Claire Palles

    (University of Oxford, Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre)

  • John R. B. Perry

    (University of Cambridge, MRC Epidemiology Unit, School of Clinical Medicine)

  • Julian Peto

    (London School of Hygiene and Tropical Medicine)

  • Loreall Pooler

    (University of Southern California, Keck School of Medicine)

  • Jennifer Prescott

    (Harvard Medical School, Channing Division of Network Medicine, Brigham and Women’s Hospital)

  • Tony Proietto

    (University of Newcastle, School of Medicine and Public Health)

  • Timothy R. Rebbeck

    (Harvard T.H. Chan School of Public Health
    Dana-Farber Cancer Institute)

  • Harvey A. Risch

    (Yale School of Public Health)

  • Peter A. W. Rogers

    (University of Melbourne, Royal Women’s Hospital, Gynaecology Research Centre)

  • Matthias Rübner

    (Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen)

  • Ingo Runnebaum

    (Jena University Hospital - Friedrich Schiller University)

  • Carlotta Sacerdote

    (Center for Cancer Prevention (CPO-Peimonte)
    Human Genetics Foundation (HuGeF))

  • Gloria E. Sarto

    (University of Wisconsin, School of Medicine and Public Health)

  • Fredrick Schumacher

    (Case Western Reserve University)

  • Rodney J. Scott

    (John Hunter Hospital, Hunter Medical Research Institute
    University of Newcastle, Centre for Information Based Medicine
    University of Newcastle, Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health
    John Hunter Hospital, Division of Molecular Medicine, Pathology North)

  • V. Wendy Setiawan

    (University of Southern California, Keck School of Medicine)

  • Mitul Shah

    (University of Cambridge, Centre for Cancer Genetic Epidemiology)

  • Xin Sheng

    (University of Southern California, Keck School of Medicine)

  • Xiao-Ou Shu

    (Vanderbilt University School of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center)

  • Melissa C. Southey

    (The University of Melbourne
    Monash University, Precision Medicine, School of Clinical Sciences at Monash Health)

  • Anthony J. Swerdlow

    (The Institute of Cancer Research
    The Institute of Cancer Research)

  • Emma Tham

    (Karolinska Institutet
    Karolinska Institutet, Clinical Genetics)

  • Jone Trovik

    (University of Bergen, Centre for Cancer Biomarkers
    Haukeland University Hospital)

  • Constance Turman

    (Harvard T.H. Chan School of Public Health)

  • Jonathan P. Tyrer

    (University of Cambridge, Centre for Cancer Genetic Epidemiology)

  • Celine Vachon

    (Mayo Clinic)

  • David VanDen Berg

    (University of Southern California, Keck School of Medicine)

  • Adriaan Vanderstichele

    (University Hospitals Leuven, Division of Gynecologic Oncology, Leuven Cancer Institute)

  • Zhaoming Wang

    (National Cancer Institute, Division of Cancer Epidemiology and Genetics)

  • Penelope M. Webb

    (QIMR Berghofer Medical Research Institute)

  • Nicolas Wentzensen

    (National Cancer Institute, Division of Cancer Epidemiology and Genetics)

  • Henrica M. J. Werner

    (University of Bergen, Centre for Cancer Biomarkers
    Haukeland University Hospital)

  • Stacey J. Winham

    (Mayo Clinic, Division of Biomedical Statistics and Informatics)

  • Alicja Wolk

    (Karolinska Institutet, Division of Nutritional Epidemiology)

  • Lucy Xia

    (University of Southern California, Keck School of Medicine)

  • Yong-Bing Xiang

    (Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, State Key Laboratory of Oncogene and Related Genes)

  • Hannah P. Yang

    (National Cancer Institute, Division of Cancer Epidemiology and Genetics)

  • Herbert Yu

    (University of Hawaii Cancer Center)

  • Wei Zheng

    (Vanderbilt University School of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center)

  • Paul D. P. Pharoah

    (University of Cambridge, Centre for Cancer Genetic Epidemiology
    University of Cambridge, Centre for Cancer Genetic Epidemiology)

  • Alison M. Dunning

    (University of Cambridge, Centre for Cancer Genetic Epidemiology)

  • Peter Kraft

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health)

  • Immaculata Vivo

    (Harvard T.H. Chan School of Public Health
    Harvard Medical School, Channing Division of Network Medicine, Brigham and Women’s Hospital)

  • Ian Tomlinson

    (University of Oxford, Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre
    University of Birmingham, Institute of Cancer and Genomic Sciences)

  • Douglas F. Easton

    (University of Cambridge, Centre for Cancer Genetic Epidemiology
    University of Cambridge, Centre for Cancer Genetic Epidemiology)

  • Amanda B. Spurdle

    (QIMR Berghofer Medical Research Institute)

  • Deborah J. Thompson

    (University of Cambridge, Centre for Cancer Genetic Epidemiology)

Abstract

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.

Suggested Citation

  • Tracy A. O’Mara & Dylan M. Glubb & Frederic Amant & Daniela Annibali & Katie Ashton & John Attia & Paul L. Auer & Matthias W. Beckmann & Amanda Black & Manjeet K. Bolla & Hiltrud Brauch & Hermann Bren, 2018. "Identification of nine new susceptibility loci for endometrial cancer," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05427-7
    DOI: 10.1038/s41467-018-05427-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-05427-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-05427-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05427-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.