Identification of nine new susceptibility loci for endometrial cancer

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 Brenner, Louise Brinton, Daniel D. Buchanan, Barbara Burwinkel, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, Maxine M. Chen, Timothy H. T. Cheng, Christine L. Clarke, Mark Clendenning, Linda S. Cook, Fergus J. Couch, Angela Cox, Marta Crous-Bous, Kamila Czene, Felix Day, Joe Dennis, Jeroen Depreeuw, Jennifer Anne Doherty, Thilo Dörk, Sean C. Dowdy, Matthias Dürst, Arif B. Ekici, Peter A. Fasching, Brooke L. Fridley, Christine M. Friedenreich, Lin Fritschi, Jenny Fung, Montserrat García-Closas, Mia M. Gaudet, Graham G. Giles, Ellen L. Goode, Maggie Gorman, Christopher A. Haiman, Per Hall, Susan E. Hankison, Catherine S. Healey, Alexander Hein, Peter Hillemanns, Shirley Hodgson, Erling A. Hoivik, Elizabeth G. Holliday, John L. Hopper, David J. Hunter, Angela Jones, Camilla Krakstad, Vessela N. Kristensen, Diether Lambrechts, Loic Le Marchand, Xiaolin Liang, Annika Lindblom, Jolanta Lissowska, Jirong Long, Lingeng Lu, Anthony M. Magliocco, Lynn Martin, Mark McEvoy, Alfons Meindl, Kyriaki Michailidou, Roger L. Milne, Miriam Mints, Grant W. Montgomery, Rami Nassir, Håkan Olsson, Irene Orlow, Geoffrey Otton, Claire Palles, John R. B. Perry, Julian Peto, Loreall Pooler, Jennifer Prescott, Tony Proietto, Timothy R. Rebbeck, Harvey A. Risch, Peter A. W. Rogers, Matthias Rübner, Ingo Runnebaum, Carlotta Sacerdote, Gloria E. Sarto, Fredrick Schumacher, Rodney J. Scott, V. Wendy Setiawan, Mitul Shah, Xin Sheng, Xiao-Ou Shu, Melissa C. Southey, Anthony J. Swerdlow, Emma Tham, Jone Trovik, Constance Turman, Jonathan P. Tyrer, Celine Vachon, David VanDen Berg, Adriaan Vanderstichele, Zhaoming Wang, Penelope M. Webb, Nicolas Wentzensen, Henrica M. J. Werner, Stacey J. Winham, Alicja Wolk, Lucy Xia, Yong-Bing Xiang, Hannah P. Yang, Herbert Yu, Wei Zheng, Paul D. P. Pharoah, Alison M. Dunning, Peter Kraft, Immaculata Vivo, Ian Tomlinson, Douglas F. Easton, Amanda B. Spurdle () and Deborah J. Thompson ()
Additional contact information
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
John Attia: John Hunter Hospital, Hunter Medical Research Institute
Paul L. Auer: Fred Hutchinson Cancer Research Center
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
Hermann Brenner: German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK)
Louise Brinton: National Cancer Institute, Division of Cancer Epidemiology and Genetics
Daniel D. Buchanan: The University of Melbourne
Barbara Burwinkel: University of Heidelberg
Jenny Chang-Claude: German Cancer Research Center (DKFZ)
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
Linda S. Cook: University of New Mexico, University of New Mexico Health Sciences Center
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
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
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
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
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
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
Susan E. Hankison: Harvard Medical School, Channing Division of Network Medicine, Brigham and Women’s Hospital
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
Elizabeth G. Holliday: John Hunter Hospital, Hunter Medical Research Institute
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
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
Vessela N. Kristensen: Oslo University Hospital, Radiumhospitalet, Institute for Cancer Research
Diether Lambrechts: University of Leuven, Laboratory for Translational Genetics
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
Roger L. Milne: The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health
Miriam Mints: Karolinska Institutet
Grant W. Montgomery: QIMR Berghofer Medical Research Institute
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
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)
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
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
Anthony J. Swerdlow: The Institute of Cancer Research
Emma Tham: Karolinska Institutet
Jone Trovik: University of Bergen, Centre for Cancer Biomarkers
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
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
Alison M. Dunning: University of Cambridge, Centre for Cancer Genetic Epidemiology
Peter Kraft: Harvard T.H. Chan School of Public Health
Immaculata Vivo: Harvard T.H. Chan School of Public Health
Ian Tomlinson: University of Oxford, Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre
Douglas F. Easton: 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

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05427-7

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