Genome-wide Association Study of Subtype-Specific Epithelial Ovarian Cancer Risk Alleles Using Pooled DNA

Madalene A Earp; Linda E Kelemen; Anthony M Magliocco; Kenneth D Swenerton; Georgia Chenevix–Trench; Yi Lu; Alexander Hein; Arif B Ekici; Matthias W Beckmann; Peter A Fasching; Diether Lambrechts; Evelyn Despierre; Ignace Vergote; Sandrina Lambrechts; Jennifer A Doherty; Mary Anne Rossing; Jenny Chang-Claude; Anja Rudolph; Grace Friel; Kirsten B Moysich; Kunle Odunsi; Lara Sucheston-Campbell; Galina Lurie; Marc T Goodman; Michael E Carney; Pamela J Thompson; Ingo B Runnebaum; Matthias Dürst; Peter Hillemanns; Thilo Dörk; Natalia Antonenkova; Natalia Bogdanova; Arto Leminen; Heli Nevanlinna; Liisa M Pelttari; Ralf Butzow; Clareann H Bunker; Francesmary Modugno; Robert P Edwards; Roberta B Ness; Andreas du Bois; Florian Heitz; Ira Schwaab; Philipp Harter; Beth Y Karlan; Christine Walsh; Jenny Lester; Allan Jensen; Susanne K Kjær; Claus K Høgdall; Estrid Høgdall; Lene Lundvall; Thomas A Sellers; Brooke L Fridley; Ellen L Goode; Julie M Cunningham; Robert A Vierkant; Graham G Giles; Laura Baglietto; Gianluca Severi; Melissa C Southey; Dong Liang; Xifeng Wu; Karen Lu; Michelle A.T Hildebrandt; Douglas A Levine; Maria Bisogna; Joellen M Schildkraut; Edwin S Iversen; Rachel Palmieri Weber; Andrew Berchuck; Daniel W Cramer; Kathryn L Terry; Elizabeth M Poole; Shelley S Tworoger; Elisa V Bandera; Urmila Chandran; Irene Orlow; Sara H Olson; Elisabeth Wik; Helga B Salvesen; Line Bjorge; Mari K Halle; Anne M van Altena; Katja K.H Aben; Lambertus A Kiemeney; Leon F.A.G Massuger; Tanja Pejovic; Yukie T Bean; Cezary Cybulski; Jacek Gronwald; Jan Lubinski; Nicolas Wentzensen; Louise A Brinton; Jolanta Lissowska; Montserrat Garcia–Closas; Ed Dicks; Joe Dennis; Douglas F Easton; Honglin Song; Jonathan P Tyrer; Paul D. P Pharoah; Diana Eccles; Ian G Campbell; Alice S Whittemore; Valerie McGuire; Weiva Sieh; Joseph H Rothstein; James M Flanagan; James Paul; Robert Brown; Catherine M Phelan; Harvey A Risch; John R McLaughlin; Steven A Narod; Argyrios Ziogas; Hoda Anton-Culver; Aleksandra Gentry-Maharaj; Usha Menon; Simon A Gayther; Susan J Ramus; Anna H Wu; Celeste L Pearce; Malcolm C Pike; Agnieszka Dansonka-Mieszkowska; Iwona K Rzepecka; Lukasz M Szafron; Jolanta Kupryjanczyk; Linda S Cook; Australian Ovarian Canc Study Grp; Nhu D Le; Angela Brooks–Wilson

doi:10.1007/s00439-013-1383-3

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Genome-wide Association Study of Subtype-Specific Epithelial Ovarian Cancer Risk Alleles Using Pooled DNA

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Genome-wide Association Study of Subtype-Specific Epithelial Ovarian Cancer Risk Alleles Using Pooled DNA

Madalene A Earp, Linda E Kelemen, Anthony M Magliocco, Kenneth D Swenerton, Georgia Chenevix–Trench, Yi Lu, Alexander Hein, Arif B Ekici, Matthias W Beckmann, Peter A Fasching, …

Human genetics, Vol.133(5), pp.481-497

05/2014

DOI: https://doi.org/10.1007/s00439-013-1383-3

PMCID: PMC4063682

PMID: 24190013

Abstract

BPIL2

clear cell

endometrioid

histological subtype

mucinous

serous

Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS (56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low malignant potential (LMP) serous, and 24 for invasive serous EOC), selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95% confidence intervals are reported. Nine variants tagging 6 loci were associated with subtype-specific EOC risk at P<0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR=1.17, P=0.029, n=1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P=0.014, n=2,903 cases), and C22orf26 /BPIL2 for LMP serous EOC (rs9609538, OR=0.86, P=0.0043, n=892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR=0.84, P=0.0007) and LMP serous EOC risk remained statistically significant at P<0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes.

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Title: Genome-wide Association Study of Subtype-Specific Epithelial Ovarian Cancer Risk Alleles Using Pooled DNA
Creators: Madalene A Earp - Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada
Linda E Kelemen - Alberta Health Services-Cancer Care, Department of Population Health Research, Calgary, AB, Canada
Anthony M Magliocco - Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
Kenneth D Swenerton - Department of Medicine, University of British Columbia, Vancouver, BC, Canada
Georgia Chenevix–Trench - Genetics and Population Health, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Yi Lu - Genetics and Population Health, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Alexander Hein - Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, Germany
Arif B Ekici - Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
Matthias W Beckmann - Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, Germany
Peter A Fasching - Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, Germany
Diether Lambrechts - Vesalius Research Center, VIB, Leuven, Belgium
Evelyn Despierre - Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, Leuven Cancer Institute, Leuven, Belgium
Ignace Vergote - Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, Leuven Cancer Institute, Leuven, Belgium
Sandrina Lambrechts - Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, Leuven Cancer Institute, Leuven, Belgium
Jennifer A Doherty - Section of Biostatistics and Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
Mary Anne Rossing - Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Jenny Chang-Claude - German Cancer Research Center, Division of Cancer Epidemiology, Heidelberg, Germany
Anja Rudolph - German Cancer Research Center, Division of Cancer Epidemiology, Heidelberg, Germany
Grace Friel - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
Kirsten B Moysich - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
Kunle Odunsi - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
Lara Sucheston-Campbell - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
Galina Lurie - Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA
Marc T Goodman - Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Michael E Carney - Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA
Pamela J Thompson - Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Ingo B Runnebaum - Department of Obstetrics and Gynaecology, Jena University Hospital – Friedrich Schiller University Jena, Jena, Germany
Matthias Dürst - Department of Obstetrics and Gynaecology, Jena University Hospital – Friedrich Schiller University Jena, Jena, Germany
Peter Hillemanns - Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany
Thilo Dörk - Gynaecology Research Unit, Hannover Medical School, Hannover, Germany
Natalia Antonenkova - Aleksandrov Byelorussian Institute for Oncology and Medical Radiology, Minsk, Belarus
Natalia Bogdanova - Gynaecology Research Unit, Hannover Medical School, Hannover, Germany
Arto Leminen - Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
Heli Nevanlinna - Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
Liisa M Pelttari - Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
Ralf Butzow - Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
Clareann H Bunker - Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
Francesmary Modugno - Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
Robert P Edwards - Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA
Roberta B Ness - The University of Texas School of Public Health, Houston, TX, USA
Andreas du Bois - Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens Stiftung/Knappschaft GmbH, Essen, Germany
Florian Heitz - Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens Stiftung/Knappschaft GmbH, Essen, Germany
Ira Schwaab - Institut für Humangenetik, Wiesbaden, Germany
Philipp Harter - Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens Stiftung/Knappschaft GmbH, Essen, Germany
Beth Y Karlan - Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Christine Walsh - Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Jenny Lester - Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Allan Jensen - Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
Susanne K Kjær - Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
Claus K Høgdall - Department of Gynecology, Copenhagen University Hospital Rigshospitalet, Denmark
Estrid Høgdall - Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
Lene Lundvall - Department of Gynecology, Copenhagen University Hospital Rigshospitalet, Denmark
Thomas A Sellers - Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA
Brooke L Fridley - Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA
Ellen L Goode - Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA
Julie M Cunningham - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Robert A Vierkant - Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
Graham G Giles - Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia and Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Melbourne, VIC, Australia
Laura Baglietto - Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia and Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Melbourne, VIC, Australia
Gianluca Severi - Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia and Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Melbourne, VIC, Australia
Melissa C Southey - Department of Pathology, The University of Melbourne, VIC, Australia
Dong Liang - College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA
Xifeng Wu - Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Karen Lu - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Michelle A.T Hildebrandt - Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Douglas A Levine - Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Maria Bisogna - Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Joellen M Schildkraut - Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA
Edwin S Iversen - Cancer Control and Population Sciences, Duke Cancer Institute, Durham, NC, USA
Rachel Palmieri Weber - Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA
Andrew Berchuck - Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA
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
Elizabeth M Poole - Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
Shelley S Tworoger - Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
Elisa V Bandera - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
Urmila Chandran - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
Irene Orlow - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Sara H Olson - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Elisabeth Wik - Department of Pathology, Haukeland University Hospital, Bergen, Norway
Helga B Salvesen - Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway
Line Bjorge - Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway
Mari K Halle - Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway
Anne M van Altena - Department of Gynecology, Radboud University Medical Centre, Nijmegen, Netherlands
Katja K.H Aben - Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands
Lambertus A Kiemeney - Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands
Leon F.A.G Massuger - Department of Gynecology, Radboud University Medical Centre, Nijmegen, Netherlands
Tanja Pejovic - Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA
Yukie T Bean - Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA
Cezary Cybulski - International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
Jacek Gronwald - International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
Jan Lubinski - International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
Nicolas Wentzensen - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Louise A Brinton - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Jolanta Lissowska - Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Montserrat Garcia–Closas - Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK and Breakthrough Breast Cancer Research Centre, London, UK
Ed Dicks - Department of Oncology, University of Cambridge, Cambridge, UK
Joe Dennis - Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
Douglas F Easton - Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
Honglin Song - Department of Oncology, University of Cambridge, Cambridge, UK
Jonathan P Tyrer - Department of Oncology, University of Cambridge, Cambridge, UK
Paul D. P Pharoah - Department of Oncology, University of Cambridge, Cambridge, UK
Diana Eccles - Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, UK
Ian G Campbell - Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
Alice S Whittemore - Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Palo Alto, CA, USA
Valerie McGuire - Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Palo Alto, CA, USA
Weiva Sieh - Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Palo Alto, CA, USA
Joseph H Rothstein - Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Palo Alto, CA, USA
James M Flanagan - Department of Surgery and Cancer, Imperial College London, London, UK
James Paul - The Beatson West of Scotland Cancer Centre, Glasgow, UK
Robert Brown - Department of Surgery and Cancer, Imperial College London, London, UK
Catherine M Phelan - Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA
Harvey A Risch - Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA
John R McLaughlin - Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
Steven A Narod - Women's College Research Institute, University of Toronto, Toronto, ON, Canada
Argyrios Ziogas - Department of Epidemiology, Center for Cancer Genetics Research and Prevention, School of Medicine, University of California–Irvine, Irvine, CA, USA
Hoda Anton-Culver - Department of Epidemiology, Center for Cancer Genetics Research and Prevention, School of Medicine, University of California–Irvine, Irvine, CA, USA
Aleksandra Gentry-Maharaj - Gynaecological Cancer Research Centre, Women's Cancer, University College London Elizabeth Garrett Anderson Institute for Women's Health, London, UK
Usha Menon - Gynaecological Cancer Research Centre, Women's Cancer, University College London Elizabeth Garrett Anderson Institute for Women's Health, London, UK
Simon A Gayther - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
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
Celeste L Pearce - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Malcolm C Pike - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Agnieszka Dansonka-Mieszkowska - Department of Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Iwona K Rzepecka - Department of Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Lukasz M Szafron - Department of Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Jolanta Kupryjanczyk - Department of Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Linda S Cook - Alberta Health Services-Cancer Care, Department of Population Health Research, Calgary, AB, Canada
Australian Ovarian Canc Study Grp
Nhu D Le - Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada
Angela Brooks–Wilson - Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada
Publication Details: Human genetics, Vol.133(5), pp.481-497
Date published: 05/2014
Academic Unit: Cancer Epidemiology and Health Outcomes
Language: English
Resource Type: Journal article
Identifiers: 991031665292804646