Five endometrial cancer risk loci identified through genome-wide association analysis

Research output: Contribution to journalArticle


  • Timothy Ht Cheng
  • Deborah J Thompson
  • Tracy A O'Mara
  • Jodie N Painter
  • Dylan M Glubb
  • Susanne Flach
  • Annabelle Lewis
  • Juliet D French
  • Luke Freeman-Mills
  • David Church
  • Maggie Gorman
  • Lynn Martin
  • Shirley Hodgson
  • Penelope M Webb
  • John Attia
  • Elizabeth G Holliday
  • Mark McEvoy
  • Rodney J Scott
  • Anjali K Henders
  • Nicholas G Martin
  • Grant W Montgomery
  • Dale R Nyholt
  • Shahana Ahmed
  • Catherine S Healey
  • Mitul Shah
  • Joe Dennis
  • Peter A Fasching
  • Matthias W Beckmann
  • Alexander Hein
  • Arif B Ekici
  • Per Hall
  • Kamila Czene
  • Hatef Darabi
  • Jingmei Li
  • Thilo Dörk
  • Matthias Dürst
  • Peter Hillemanns
  • Ingo Runnebaum
  • Frederic Amant
  • Stefanie Schrauwen
  • Hui Zhao
  • Diether Lambrechts
  • Jeroen Depreeuw
  • Sean C Dowdy
  • Ellen L Goode
  • Brooke L Fridley
  • Stacey J Winham
  • Tormund S Njølstad
  • Helga B Salvesen
  • National Study of Endometrial Cancer Genetics Group (NSECG)
  • Ian Tomlinson

Colleges, School and Institutes

External organisations

  • Department of Clinical Genetics, St George's, University of London, London, UK.
  • Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, NSW, Australia.
  • School of Clinical Sciences and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
  • Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Hannover Medical School, Gynaecology Research Unit, Hannover, Germany.
  • Department of Gynaecology, Jena University Hospital - Friedrich Schiller University, Jena, Germany.
  • Hannover Medical School, Clinics of Gynaecology and Obstetrics, Hannover, Germany.
  • Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals, KU Leuven - University of Leuven, Belgium.
  • Laboratory for Translational Genetics, Department of Oncology, University Hospitals Leuven, Leuven, Belgium.
  • Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN, USA.
  • Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA.
  • Wellcome Trust Centre for Human Genetics, University of Oxford
  • University of Cambridge
  • Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, NSW 2308, Australia
  • Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.


We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.


Original languageEnglish
Pages (from-to)667-674
Number of pages8
JournalNature Genetics
Issue number6
Early online date2 May 2016
Publication statusPublished - Jun 2016


  • Chromosomes, Human, Pair 8, Endometrial Neoplasms, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Journal Article, Meta-Analysis