Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

Gabriel Cuellar-Partida; Yi Lu; Suzanne C Dixon; Peter A Fasching; Alexander Hein; Stefanie Burghaus; Matthias W Beckmann; Diether Lambrechts; Els Van Nieuwenhuysen; Ignace Vergote; Adriaan Vanderstichele; Jennifer Anne Doherty; Mary Anne Rossing; Jenny Chang-Claude; Anja Rudolph; Shan Wang-Gohrke; Marc T Goodman; Natalia Bogdanova; Thilo Dörk; Matthias Dürst; Peter Hillemanns; Ingo B Runnebaum; Natalia Antonenkova; Ralf Butzow; Arto Leminen; Heli Nevanlinna; Liisa M Pelttari; Robert P Edwards; Joseph L Kelley; Francesmary Modugno; Kirsten B Moysich; Roberta B Ness; Rikki Cannioto; Estrid Høgdall; Claus Høgdall; Allan Jensen; Graham G Giles; Fiona Bruinsma; Susanne K Kjaer; Michelle A T Hildebrandt; Dong Liang; Karen H Lu; Xifeng Wu; Maria Bisogna; Fanny Dao; Douglas A Levine; Daniel W Cramer; Kathryn L Terry; Shelley S Tworoger; Meir Stampfer; Stacey Missmer; Line Bjorge; Helga B Salvesen; Reidun K Kopperud; Katharina Bischof; Katja K H Aben; Lambertus A Kiemeney; Leon F A G Massuger; Angela Brooks-Wilson; Sara H Olson; Valerie McGuire; Joseph H Rothstein; Weiva Sieh; Alice S Whittemore; Linda S Cook; Nhu D Le; C Blake Gilks; Jacek Gronwald; Anna Jakubowska; Jan Lubiński; Tomasz Kluz; Honglin Song; Jonathan P Tyrer; Nicolas Wentzensen; Louise Brinton; Britton Trabert; Jolanta Lissowska; John R McLaughlin; Steven A Narod; Catherine Phelan; Hoda Anton-Culver; Argyrios Ziogas; Diana Eccles; Ian Campbell; Simon A Gayther; Aleksandra Gentry-Maharaj; Usha Menon; Susan J Ramus; Anna H Wu; Agnieszka Dansonka-Mieszkowska; Jolanta Kupryjanczyk; Agnieszka Timorek; Lukasz Szafron; Julie M Cunningham; Brooke L Fridley; Stacey J Winham; Elisa V Bandera; Elizabeth M Poole; Terry K Morgan; Ellen L Goode; Joellen M Schildkraut; Celeste L Pearce; Andrew Berchuck; Paul D P Pharoah; Penelope M Webb; Georgia Chenevix-Trench; Harvey A Risch; Stuart MacGregor; Australian Ovarian Cancer Study

doi:10.1007/s00439-016-1663-9

Back

Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

Journal article

Open access

Peer reviewed

Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

Gabriel Cuellar-Partida, Yi Lu, Suzanne C Dixon, Peter A Fasching, Alexander Hein, Stefanie Burghaus, Matthias W Beckmann, Diether Lambrechts, Els Van Nieuwenhuysen, Ignace Vergote, …

Human genetics, Vol.135(7), pp.741-756

07/2016

DOI: https://doi.org/10.1007/s00439-016-1663-9

PMCID: PMC4976079

PMID: 27075448

Abstract

Carcinoma, Ovarian Epithelial

Female

Genotype

Humans

Neoplasms, Glandular and Epithelial - classification

Neoplasms, Glandular and Epithelial - genetics

Neoplasms, Glandular and Epithelial - pathology

Ovarian Neoplasms - classification

Ovarian Neoplasms - genetics

Ovarian Neoplasms - pathology

Pathology, Molecular

Polymorphism, Single Nucleotide - genetics

Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.

Files and links (1)

url

https://doi.org/10.1007/s00439-016-1663-9View

Version of Record (VoR) Open

Metrics

19 Record Views

17 Times Cited - Web of Science

See more details

Details

Title: Assessing the genetic architecture of epithelial ovarian cancer histological subtypes
Creators: Gabriel Cuellar-Partida - School of Medicine, University of Queensland, St Lucia, QLD, 4072, Australia. gabriel.cuellar@qimrberghofer.edu.au
Yi Lu - Statistical Genetics, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Australia
Suzanne C Dixon - School of Public Health, University of Queensland, Herston, QLD 4006, Australia
Peter A Fasching - Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Universitaetsstrasse 21-23, 91054, Erlangen, Germany
Alexander Hein - Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Universitaetsstrasse 21-23, 91054, Erlangen, Germany
Stefanie Burghaus - Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Universitaetsstrasse 21-23, 91054, Erlangen, Germany
Matthias W Beckmann - Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Universitaetsstrasse 21-23, 91054, Erlangen, Germany
Diether Lambrechts - Vesalius Research Center, VIB, Louvain, Belgium
Els Van Nieuwenhuysen - Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Louvain, Belgium
Ignace Vergote - Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Louvain, Belgium
Adriaan Vanderstichele - Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Louvain, Belgium
Jennifer Anne Doherty - Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA
Mary Anne Rossing - Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Jenny Chang-Claude - University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Anja Rudolph - Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
Shan Wang-Gohrke - Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany
Marc T Goodman - Department of Biomedical Sciences, Cedars-Sinai Medical Center, Community and Population Health Research Institute, Los Angeles, CA, USA
Natalia Bogdanova - Radiation Oncology Research Unit, Hannover Medical School, Hannover, Germany
Thilo Dörk - Gynaecology Research Unit, Hannover Medical School, Hannover, Germany
Matthias Dürst - Department of Gynecology, Jena-University Hospital-Friedrich Schiller University, Jena, Germany
Peter Hillemanns - Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany
Ingo B Runnebaum - Department of Gynecology, Jena-University Hospital-Friedrich Schiller University, Jena, Germany
Natalia Antonenkova - N.N. Alexandrov National Cancer Centre of Belarus, Minsk, Belarus
Ralf Butzow - Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Arto Leminen - Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Heli Nevanlinna - Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Liisa M Pelttari - Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Robert P Edwards - Womens Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
Joseph L Kelley - Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Francesmary Modugno - Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
Kirsten B Moysich - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
Roberta B Ness - The University of Texas School of Public Health, Houston, TX, USA
Rikki Cannioto - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
Estrid Høgdall - Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Claus Høgdall - Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Allan Jensen - Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
Graham G Giles - Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia
Fiona Bruinsma - Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia
Susanne K Kjaer - Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Michelle A T Hildebrandt - Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Dong Liang - College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA
Karen H Lu - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Xifeng Wu - Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Maria Bisogna - Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Fanny Dao - Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Douglas A Levine - Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Daniel W Cramer - Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA
Kathryn L Terry - Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA
Shelley S Tworoger - Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Meir Stampfer - Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Stacey Missmer - Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Line Bjorge - Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
Helga B Salvesen - Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
Reidun K Kopperud - Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
Katharina Bischof - Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
Katja K H Aben - Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands
Lambertus A Kiemeney - Radboud University Medical Centre, RADBOUD Institute for Health Sciences, Nijmegen, The Netherlands
Leon F A G Massuger - Department of Obstetrics and Gynaecology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands
Angela Brooks-Wilson - Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada
Sara H Olson - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Valerie McGuire - Department of Health Research and Policy-Epidemiology, Stanford University School of Medicine, Stanford, CA, USA
Joseph H Rothstein - Department of Health Research and Policy-Epidemiology, Stanford University School of Medicine, Stanford, CA, USA
Weiva Sieh - Department of Health Research and Policy-Epidemiology, Stanford University School of Medicine, Stanford, CA, USA
Alice S Whittemore - Department of Health Research and Policy-Epidemiology, Stanford University School of Medicine, Stanford, CA, USA
Linda S Cook - Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA
Nhu D Le - Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada
C Blake Gilks - Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
Jacek Gronwald - Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
Anna Jakubowska - Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
Jan Lubiński - Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
Tomasz Kluz - Faculty of Medicine, Institute of Midwifery and Emergency Medicine, Clinic of Obstetrics and Gynecology, Frederick Chopin Clinical Provincial Hospital No 1, University of Rzeszów, Rzeszow, Poland
Honglin Song - Department of Oncology, The Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
Jonathan P Tyrer - Department of Oncology, The Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
Nicolas Wentzensen - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Louise Brinton - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Britton Trabert - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Jolanta Lissowska - Department of Cancer Epidemiology and Prevention, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
John R McLaughlin - Public Health Ontario, Toronto, ON, Canada
Steven A Narod - Women's College Research Institute, University of Toronto, Toronto, ON, Canada
Catherine Phelan - Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA
Hoda Anton-Culver - Center for Cancer Genetics Research and Prevention, School of Medicine, University of California Irvine, Irvine, CA, USA
Argyrios Ziogas - Department of Epidemiology, University of California Irvine, Irvine, CA, USA
Diana Eccles - Faculty of Medicine, University of Southampton, Southampton, UK
Ian Campbell - Research Division, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Australia
Simon A Gayther - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Aleksandra Gentry-Maharaj - Women's Cancer, Institute for Women's Health, University College London, London, UK
Usha Menon - Women's Cancer, Institute for Women's Health, University College London, London, UK
Susan J Ramus - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Anna H Wu - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Agnieszka Dansonka-Mieszkowska - Department of Pathology and Laboratory Diagnostics, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Jolanta Kupryjanczyk - Department of Pathology and Laboratory Diagnostics, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Agnieszka Timorek - Department of Obstetrics, Gynaecology and Oncology, IInd Faculty of Medicine, Warsaw Medical University and Brodnowski Hospital, Warsaw, Poland
Lukasz Szafron - Department of Pathology and Laboratory Diagnostics, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Julie M Cunningham - Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Brooke L Fridley - Department of Biostatistics, University of Kansas, Kansas City, KS, USA
Stacey J Winham - Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Elisa V Bandera - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
Elizabeth M Poole - Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Terry K Morgan - Department of Gynaecology, OHSU, Portland, OR, USA
Ellen L Goode - Division of Epidemiology, Department of Health Science Research, Mayo Clinic, Rochester, MN, USA
Joellen M Schildkraut - Department of Public Health Sciences, University of Virginia, Virginia, USA
Celeste L Pearce - Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
Andrew Berchuck - Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA
Paul D P Pharoah - Department of Oncology, The Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
Penelope M Webb - School of Public Health, University of Queensland, Herston, QLD 4006, Australia
Georgia Chenevix-Trench - Cancer Genetics, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Australia
Harvey A Risch - Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA
Stuart MacGregor - Statistical Genetics, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Australia. Stuart.MacGregor@qimrberghofer.edu.au
Australian Ovarian Cancer Study
Publication Details: Human genetics, Vol.135(7), pp.741-756
Date published: 07/2016
Grant note: R03 CA113148 / NCI NIH HHS R01 CA058860 / NCI NIH HHS 10119 / Cancer Research UK R01 CA063678 / NCI NIH HHS R01 CA112523 / NCI NIH HHS R01 CA149429 / NCI NIH HHS R01 CA114343 / NCI NIH HHS R01 CA063682 / NCI NIH HHS R01 CA058598 / NCI NIH HHS 10124 / Cancer Research UK R01 CA067262 / NCI NIH HHS UL1 TR001863 / NCATS NIH HHS P30 CA076292 / NCI NIH HHS R01 CA074850 / NCI NIH HHS R01 CA054419 / NCI NIH HHS R01 CA050385 / NCI NIH HHS K07 CA092044 / NCI NIH HHS P01 CA087969 / NCI NIH HHS P30 CA046592 / NCI NIH HHS P30 CA008748 / NCI NIH HHS R01 CA087538 / NCI NIH HHS P50 CA136393 / NCI NIH HHS R01 CA122443 / NCI NIH HHS R01 CA049449 / NCI NIH HHS R01 CA126841 / NCI NIH HHS P30 CA014089 / NCI NIH HHS P30 CA072720 / NCI NIH HHS
Academic Unit: Cancer Epidemiology and Health Outcomes
Language: English
Resource Type: Journal article
Identifiers: 991031665812404646