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 De Vivo; Ian Tomlinson; Douglas F Easton; Amanda B Spurdle; Deborah J Thompson; et al

doi:10.1038/s41467-018-05427-7

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Identification of nine new susceptibility loci for endometrial cancer

Journal article

Open access

Peer reviewed

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, …

Nature communications, Vol.9(1), pp.3166-12

09/08/2018

DOI: https://doi.org/10.1038/s41467-018-05427-7

PMCID: PMC6085317

PMID: 30093612

Abstract

Alleles

Biomarkers, Tumor - genetics

Chromatin - chemistry

Endometrial Neoplasms - genetics

Female

Gene Frequency

Genetic Predisposition to Disease

Genome-Wide Association Study

Genotype

Humans

Polymorphism, Single Nucleotide

Quantitative Trait Loci

Risk Factors

Signal Transduction

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.

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Title: Identification of nine new susceptibility loci for endometrial cancer
Creators - without role: Tracy A O'Mara - QIMR Berghofer Medical Research Institute
Dylan M Glubb - QIMR Berghofer Medical Research Institute
Frederic Amant - KU Leuven
Daniela Annibali - KU Leuven
Katie Ashton - University of Newcastle Australia
John Attia - University of Newcastle Australia
Paul L Auer - University of Wisconsin–Milwaukee
Matthias W Beckmann - Comprehensive Cancer Center Erlangen
Amanda Black - National Cancer Institute
Manjeet K Bolla - University of Cambridge
Hiltrud Brauch - Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
Hermann Brenner - German Cancer Research Center
Louise Brinton - National Cancer Institute
Daniel D Buchanan - University of Melbourne
Barbara Burwinkel - Heidelberg University
Jenny Chang-Claude - German Cancer Research Center
Stephen J Chanock - National Cancer Institute
Chu Chen - Fred Hutch Cancer Center
Maxine M Chen - Harvard University
Timothy H T Cheng - Wellcome Centre for Human Genetics
Christine L Clarke - University of Sydney
Mark Clendenning - University of Melbourne
Linda S Cook - Alberta Health Services
Fergus J Couch - Mayo Clinic
Angela Cox - University of Sheffield
Marta Crous-Bous - Harvard University
Kamila Czene - Karolinska Institutet
Felix Day - MRC Epidemiology Unit
Joe Dennis - University of Cambridge
Jeroen Depreeuw - KU Leuven
Jennifer Anne Doherty - Huntsman Cancer Institute
Thilo Dörk - Medizinische Hochschule Hannover
Sean C Dowdy - Mayo Clinic
Matthias Dürst - Friedrich Schiller University Jena
Arif B Ekici - Comprehensive Cancer Center Erlangen
Peter A Fasching - Comprehensive Cancer Center Erlangen
Brooke L Fridley - University of Kansas Medical Center
Christine M Friedenreich - Alberta Health Services
Lin Fritschi - Curtin University
Jenny Fung - University of Queensland
Montserrat García-Closas - National Cancer Institute
Mia M Gaudet - American Cancer Society
Graham G Giles - Cancer Council Victoria
Ellen L Goode - Mayo Clinic
Maggie Gorman - Wellcome Centre for Human Genetics
Christopher A Haiman - University of Southern California
Per Hall - Karolinska Institutet
Susan E Hankison - Brigham and Women's Hospital
Catherine S Healey - University of Cambridge
Alexander Hein - Comprehensive Cancer Center Erlangen
Peter Hillemanns - Medizinische Hochschule Hannover
Shirley Hodgson - St George's, University of London
Erling A Hoivik - University of Bergen
Elizabeth G Holliday - University of Newcastle Australia
John L Hopper - University of Melbourne
David J Hunter - Harvard University
Angela Jones - Wellcome Centre for Human Genetics
Camilla Krakstad - University of Bergen
Vessela N Kristensen - Oslo University Hospital
Diether Lambrechts - KU Leuven
Loic Le Marchand - University of Hawaii System
Xiaolin Liang - Memorial Sloan Kettering Cancer Center
Annika Lindblom - Karolinska Institutet
Jolanta Lissowska - The Maria Sklodowska-Curie National Research Institute of Oncology
Jirong Long - Vanderbilt University
Lingeng Lu - Yale University
Anthony M Magliocco - Moffitt Cancer Center
Lynn Martin - University of Birmingham
Mark McEvoy - University of Newcastle Australia
Alfons Meindl - Ludwig-Maximilians-Universität München
Kyriaki Michailidou - University of Cambridge
Roger L Milne - University of Melbourne
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 Australia
Claire Palles - Wellcome Centre for Human Genetics
John R B Perry - MRC Epidemiology Unit
Julian Peto - London School of Hygiene & Tropical Medicine
Loreall Pooler - University of Southern California
Jennifer Prescott - Brigham and Women's Hospital
Tony Proietto - University of Newcastle Australia
Timothy R Rebbeck - Harvard University
Harvey A Risch - Yale University
Peter A W Rogers - University of Melbourne
Matthias Rübner - Comprehensive Cancer Center Erlangen
Ingo Runnebaum - Friedrich Schiller University Jena
Carlotta Sacerdote - Italian institute for Genomic Medicine
Gloria E Sarto - University of Wisconsin–Madison
Fredrick Schumacher - Case Western Reserve University
Rodney J Scott - University of Newcastle Australia
V Wendy Setiawan - University of Southern California
Mitul Shah - University of Cambridge
Xin Sheng - University of Southern California
Xiao-Ou Shu - Vanderbilt University
Melissa C Southey - Monash University
Anthony J Swerdlow - Institute of Cancer Research
Emma Tham - Karolinska Institutet
Jone Trovik - Haukeland University Hospital
Constance Turman - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, 02115, MA, USA
Jonathan P Tyrer - University of Cambridge
Celine Vachon - Department of Health Sciences Research, Mayo Clinic, Rochester, 55905, MN, USA
David VanDen Berg - Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, 90033, CA, USA
Adriaan Vanderstichele - Department of Obstetrics and Gynaecology, University Hospitals Leuven, Division of Gynecologic Oncology, Leuven Cancer Institute, Leuven, 3000, Belgium
Zhaoming Wang - National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, 20892, MD, USA
Penelope M Webb - QIMR Berghofer Medical Research Institute
Nicolas Wentzensen - National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, 20892, MD, USA
Henrica M J Werner - Haukeland University Hospital
Stacey J Winham - Department of Health Science Research, Mayo Clinic, Division of Biomedical Statistics and Informatics, Rochester, 55905, MN, USA
Alicja Wolk - Karolinska Institutet
Lucy Xia - Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, 90033, CA, USA
Yong-Bing Xiang - Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, State Key Laboratory of Oncogene and Related Genes, Shanghai, China
Hannah P Yang - National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, 20892, MD, USA
Herbert Yu - University of Hawaii System
Wei Zheng - Vanderbilt University School of Medicine
Paul D P Pharoah - University of Cambridge
Alison M Dunning - University of Cambridge
Peter Kraft - Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, 02115, MA, USA
Immaculata De Vivo - Brigham and Women's Hospital
Ian Tomlinson - University of Birmingham
Douglas F Easton - University of Cambridge
Amanda B Spurdle - QIMR Berghofer Medical Research Institute
Deborah J Thompson - University of Cambridge
et al
Publication Details: Nature communications, Vol.9(1), pp.3166-12
Grant note: UM1 CA182910 / NCI NIH HHS HHSN271201100004C / NIA NIH HHS Wellcome Trust HHSN268201100004I / NHLBI NIH HHS N01 HD023166 / NICHD NIH HHS HHSN268201600003C / NHLBI NIH HHS R01 CA054281 / NCI NIH HHS R01 CA105212 / NCI NIH HHS R03 CA080636 / NCI NIH HHS MC_QA137853 / Medical Research Council P30 CA015083 / NCI NIH HHS HHSN268201100004C / WHI NIH HHS U19 CA148537 / NCI NIH HHS R01 CA149429 / NCI NIH HHS HHSN268201600018C / NHLBI NIH HHS HHSN268201100002C / WHI NIH HHS U19 CA148065 / NCI NIH HHS R01 CA058598 / NCI NIH HHS R01 CA128978 / NCI NIH HHS HHSN268201600002C / NHLBI NIH HHS U19 CA148112 / NCI NIH HHS HHSN268201100003C / WHI NIH HHS R01 CA077398 / NCI NIH HHS R01 CA134958 / NCI NIH HHS HHSN268201100002I / NHLBI NIH HHS HHSN268201100001C / WHI NIH HHS K05 CA092002 / NCI NIH HHS HHSN268201600001C / NHLBI NIH HHS P01 CA087969 / NCI NIH HHS P30 CA008748 / NCI NIH HHS MC_UU_12015/2 / Medical Research Council UM1 CA186107 / NCI NIH HHS R01 CA091019 / NCI NIH HHS HHSN268201100046C / NHLBI NIH HHS R37 CA054281 / NCI NIH HHS R01 CA087538 / NCI NIH HHS P50 CA136393 / NCI NIH HHS R03 CA128008 / NCI NIH HHS R01 CA082838 / NCI NIH HHS R01 CA122443 / NCI NIH HHS HHSN268201100001I / NHLBI NIH HHS HHSN268201600004C / NHLBI NIH HHS MC_PC_17228 / Medical Research Council R01 CA098346 / NCI NIH HHS R01 CA049449 / NCI NIH HHS 10118 / Cancer Research UK
Identifiers: 9931794008331
Academic Unit: Umm Al Qura University
Language: English
Resource Type: Journal article