Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Yi Lu; John R Mclaughlin; Elisa V Bandera; Gabriel Cuellar-Partida; Jodie N Painter; Dale R Nyholt; Andrew P Morris; 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; Kristine G Wicklund; Jenny Chang-Claude; Ursula Eilber; 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; 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; 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; Jan Gawełko; Honglin Song; Jonathan P Tyrer; Nicolas Wentzensen; Louise Brinton; Britton Trabert; Jolanta Lissowska; Steven A Narod; Catherine Phelan; Hoda Anton-Culver; Argyrios Ziogas; Diana Eccles; 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; Elizabeth M Poole; Terry K Morgan; Harvey A Risch; Ellen L Goode; Joellen M Schildkraut; Penelope M Webb; Celeste L Pearce; Andrew Berchuck; Paul D P Pharoah; Grant W Montgomery; Krina T Zondervan; Georgia Chenevix-Trench; Stuart MacGregor; Australian Ovarian Cancer Study

doi:10.1093/hmg/ddv306

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Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Journal article

Open access

Peer reviewed

Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Yi Lu, John R Mclaughlin, Elisa V Bandera, Gabriel Cuellar-Partida, Jodie N Painter, Dale R Nyholt, Andrew P Morris, Peter A Fasching, Alexander Hein, Stefanie Burghaus, …

Human molecular genetics, Vol.24(20), pp.5955-5964

10/15/2015

DOI: https://doi.org/10.1093/hmg/ddv306

PMCID: PMC4581608

PMID: 26231222

Abstract

Endometriosis - epidemiology

Endometriosis - genetics

Female

Genetic Association Studies

Genetic Predisposition to Disease

Humans

Oligonucleotide Array Sequence Analysis

Ovarian Neoplasms - epidemiology

Ovarian Neoplasms - genetics

Polymorphism, Single Nucleotide

Risk

Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.

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Title: Shared genetics underlying epidemiological association between endometriosis and ovarian cancer
Creators: Yi Lu - Statistical Genetics
John R Mclaughlin - Public Health Ontario, Toronto, ON, Canada
Elisa V Bandera - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
Gabriel Cuellar-Partida - Statistical Genetics
Jodie N Painter - Molecular Cancer Epidemiology
Dale R Nyholt - Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia
Andrew P Morris - Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics and Department of Biostatistics, University of Liverpool, Liverpool, UK
Peter A Fasching - Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen Nuremberg, Universitaetsstrasse 21-23, 91054 Erlangen, Germany
Alexander Hein - Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen Nuremberg, Universitaetsstrasse 21-23, 91054 Erlangen, Germany
Stefanie Burghaus - Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen Nuremberg, Universitaetsstrasse 21-23, 91054 Erlangen, Germany
Matthias W Beckmann - Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen Nuremberg, Universitaetsstrasse 21-23, 91054 Erlangen, Germany
Diether Lambrechts - Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium, Vesalius Research Center, VIB, Leuven, Belgium
Els Van Nieuwenhuysen - Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
Ignace Vergote - Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
Adriaan Vanderstichele - Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
Jennifer Anne Doherty - Department of Community and Family Medicine, Section of Biostatistics & Epidemiology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA
Mary Anne Rossing - Department of Epidemiology, University of Washington, Seattle, WA, USA, Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Kristine G Wicklund - Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Jenny Chang-Claude - Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
Ursula Eilber - Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, 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 - Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute and Department of Biomedical Sciences, Community and Population Health Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Natalia Bogdanova - Radiation Oncology Research Unit
Thilo Dörk - Gynaecology Research Unit and
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 and
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 - Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, 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 - Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, Womens Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA, 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 - Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark, Molecular Unit, Department of Pathology, Herlev Hospital, Herlev, Denmark
Allan Jensen - Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
Graham G Giles - Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia, Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia
Fiona Bruinsma - Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia
Susanne K Kjaer - Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark, Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Michelle A T Hildebrandt - Department of Epidemiology and
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 and
Maria Bisogna - Gynecology Service, Department of Surgery and
Fanny Dao - Gynecology Service, Department of Surgery and
Douglas A Levine - Gynecology Service, Department of Surgery and
Daniel W Cramer - Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA
Kathryn L Terry - Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Shelley S Tworoger - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Channing Division of Network Medicine, Department of Medicine and
Stacey Missmer - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Channing Division of Network Medicine, Department of Medicine and Department of Obstetrics and Gynecology, Gynecology and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Line Bjorge - Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway, Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
Helga B Salvesen - Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway, Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
Reidun K Kopperud - Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway, Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
Katharina Bischof - Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway, Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
Katja K H Aben - Radboud University Medical Centre, Radboud Institute for Health Sciences, Nijmegen, The Netherlands, 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 Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
Angela Brooks-Wilson - Canada's Michael Smith Genome Sciences Centre and 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
Jan Gawełko - Medical Faculty, Institute of Nursing and Health Sciences, University of Rzeszów, Rzeszów, Poland
Honglin Song - Department of Oncology and
Jonathan P Tyrer - Department of Oncology and
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 - M. Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland
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 - Department of Epidemiology and Center for Cancer Genetics Research & Prevention, School of Medicine, University of California Irvine, Irvine, CA, USA
Argyrios Ziogas - Department of Epidemiology and
Diana Eccles - Faculty of Medicine, University of Southampton, Southampton, UK
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, Gynecology 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
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 and
Elizabeth M Poole - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Channing Division of Network Medicine, Department of Medicine and
Terry K Morgan - Department of Pathology and Department of Obstetrics and Gynecology, OHSU, Portland, OR, USA
Harvey A Risch - Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA
Ellen L Goode - Division of Epidemiology, Department of Health Science Research, Mayo Clinic, Rochester, MN, USA
Joellen M Schildkraut - Department of Community and Family Medicine and Cancer Control and Population Sciences, Duke Cancer Institute, Durham, NC, USA
Penelope M Webb - Population Health Department
Celeste L Pearce - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA and
Andrew Berchuck - Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA
Paul D P Pharoah - Department of Oncology and Department of Public Health and Primary Care, The Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
Grant W Montgomery - Molecular Epidemiology and
Krina T Zondervan - Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics and Endometriosis CaRe Centre, Nuffield Dept of Obstetrics & Gynaecology, University of Oxford, Oxford, UK
Georgia Chenevix-Trench - Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia
Stuart MacGregor - Statistical Genetics, stuart.macgregor@qimrberghofer.edu.au
Australian Ovarian Cancer Study
Publication Details: Human molecular genetics, Vol.24(20), pp.5955-5964
Date published: 10/15/2015
Grant note: R01-CA017054 / NCI NIH HHS K22-CA138563 / NCI NIH HHS R01-CA122443 / NCI NIH HHS P01-CA017054 / NCI NIH HHS R01-CA083918 / NCI NIH HHS R01-CA067262 / NCI NIH HHS R01-CA050385 / NCI NIH HHS R01-CA074850 / NCI NIH HHS K07-CA80668 / NCI NIH HHS 085235 / Wellcome Trust R01-CA092044 / NCI NIH HHS R03-CA115195 / NCI NIH HHS WT098017 / Wellcome Trust R01-CA080978 / NCI NIH HHS R01-CA054419 / NCI NIH HHS R01-CA058598 / NCI NIH HHS WT085235/Z/08/Z / Wellcome Trust MO1-RR000056 / NCRR NIH HHS R01-CA063682 / NCI NIH HHS R01-CA149429 / NCI NIH HHS N01-PC035137 / NCI NIH HHS UL1 TR000005 / NCATS NIH HHS P50-CA105009 / NCI NIH HHS MOP-86727 / CIHR P01-CA087696 / NCI NIH HHS U01-CA069417 / NCI NIH HHS R01 CA087538 / NCI NIH HHS WT084766/Z/08/Z / Wellcome Trust R01-CA063678 / NCI NIH HHS R01-CA061132 / NCI NIH HHS R01-CA071766 / NCI NIH HHS K07-CA095666 / NCI NIH HHS R01-CA014089 / NCI NIH HHS UM1-CA176726 / NCI NIH HHS R01-CA049449 / NCI NIH HHS R01-CA058860 / NCI NIH HHS R01-CA126841 / NCI NIH HHS P50-CA136393 / NCI NIH HHS P30 CA015083 / NCI NIH HHS P30-CA072720 / NCI NIH HHS 10124 / Cancer Research UK R01-CA114343 / NCI NIH HHS R01-CA087538 / NCI NIH HHS 084766 / Wellcome Trust UM1-CA186107 / NCI NIH HHS P30 CA076292 / NCI NIH HHS P30-CA008748 / NCI NIH HHS R01-CA095023 / NCI NIH HHS N01-CN55424 / NCI NIH HHS R01-CA136924 / NCI NIH HHS K07-CA143047 / NCI NIH HHS R01-CA061107 / NCI NIH HHS U01-CA071966 / NCI NIH HHS P50-CA159981 / NCI NIH HHS P50 CA136393 / NCI NIH HHS P30-CA15083 / NCI NIH HHS R01-CA016056 / NCI NIH HHS R03-CA113148 / NCI NIH HHS N01-PC067010 / NCI NIH HHS N01-PC67001 / NCI NIH HHS R01-CA112523 / 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: 991031665306404646