Multicenter Study

. 2015 Mar;136(3):542-8.

doi: 10.1016/j.ygyno.2014.12.017. Epub 2014 Dec 17.

Evaluating the ovarian cancer gonadotropin hypothesis: a candidate gene study

Alice W Lee¹, Jonathan P Tyrer², Jennifer A Doherty³, Douglas A Stram¹, Jolanta Kupryjanczyk⁴, Agnieszka Dansonka-Mieszkowska⁴, Joanna Plisiecka-Halasa⁴, Beata Spiewankiewicz⁵, Emily J Myers¹; Australian Cancer Study (Ovarian Cancer); Australian Ovarian Cancer Study Group; Georgia Chenevix-Trench⁶, Peter A Fasching⁷, Matthias W Beckmann⁸, Arif B Ekici⁹, Alexander Hein⁸, Ignace Vergote¹⁰, Els Van Nieuwenhuysen¹⁰, Diether Lambrechts¹¹, Kristine G Wicklund¹², Ursula Eilber¹³, Shan Wang-Gohrke¹⁴, Jenny Chang-Claude¹³, Anja Rudolph¹³, Lara Sucheston-Campbell¹⁵, Kunle Odunsi¹⁶, Kirsten B Moysich¹⁵, Yurii B Shvetsov¹⁷, Pamela J Thompson¹⁸, Marc T Goodman¹⁸, Lynne R Wilkens¹⁷, Thilo Dörk¹⁹, Peter Hillemanns²⁰, Matthias Dürst²¹, Ingo B Runnebaum²¹, Natalia Bogdanova¹⁹, Liisa M Pelttari²², Heli Nevanlinna²², Arto Leminen²², Robert P Edwards²³, Joseph L Kelley²⁴, Philipp Harter²⁵, Ira Schwaab²⁶, Florian Heitz²⁵, Andreas du Bois²⁵, Sandra Orsulic²⁷, Jenny Lester²⁷, Christine Walsh²⁷, Beth Y Karlan²⁷, Estrid Hogdall²⁸, Susanne K Kjaer²⁹, Allan Jensen³⁰, Robert A Vierkant³¹, Julie M Cunningham³², Ellen L Goode³¹, Brooke L Fridley³³, Melissa C Southey³⁴, Graham G Giles³⁵, Fiona Bruinsma³⁶, Xifeng Wu³⁷, Michelle A T Hildebrandt³⁷, Karen Lu³⁸, Dong Liang³⁹, Maria Bisogna⁴⁰, Douglas A Levine⁴⁰, Rachel Palmieri Weber⁴¹, Joellen M Schildkraut⁴², Edwin S Iversen⁴³, Andrew Berchuck⁴⁴, Kathryn L Terry⁴⁵, Daniel W Cramer⁴⁵, Shelley S Tworoger⁴⁶, Elizabeth M Poole⁴⁶, Sara H Olson⁴⁷, Irene Orlow⁴⁷, Elisa V Bandera⁴⁸, Line Bjorge⁴⁹, Ingvild L Tangen⁴⁹, Helga B Salvesen⁴⁹, Camilla Krakstad⁴⁹, Leon F A G Massuger⁵⁰, Lambertus A Kiemeney⁵¹, Katja K H Aben⁵², Anne M van Altena⁵⁰, Yukie Bean⁵³, Tanja Pejovic⁵³, Melissa Kellar⁵³, Nhu D Le⁵⁴, Linda S Cook⁵⁵, Linda E Kelemen⁵⁶, Angela Brooks-Wilson⁵⁷, Jan Lubinski⁵⁸, Jacek Gronwald⁵⁸, Cezary Cybulski⁵⁸, Anna Jakubowska⁵⁸, Nicolas Wentzensen⁵⁹, Louise A Brinton⁵⁹, Jolanta Lissowska⁶⁰, Hannah Yang⁵⁹, Lotte Nedergaard⁶¹, Lene Lundvall⁶², Claus Hogdall⁶², Honglin Song², Ian G Campbell⁶³, Diana Eccles⁶⁴, Rosalind Glasspool⁶⁵, Nadeem Siddiqui⁶⁶, Karen Carty⁶⁵, James Paul⁶⁵, Iain A McNeish⁶⁷, Weiva Sieh⁶⁸, Valerie McGuire⁶⁸, Joseph H Rothstein⁶⁸, Alice S Whittemore⁶⁸, John R McLaughlin⁶⁹, Harvey A Risch⁷⁰, Catherine M Phelan⁷¹, Hoda Anton-Culver⁷², Argyrios Ziogas⁷³, Usha Menon⁷⁴, Susan J Ramus¹, Aleksandra Gentry-Maharaj⁷⁴, Patricia Harrington⁷⁵, Malcolm C Pike⁷⁶, Francesmary Modugno⁷⁷, Mary Anne Rossing⁷⁸, Roberta B Ness⁷⁹, Paul D P Pharoah⁸⁰, Daniel O Stram¹, Anna H Wu¹, Celeste Leigh Pearce⁸¹

Affiliations

¹ Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
² Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
³ Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
⁴ Department of Pathology, Institute of Oncology, Warsaw, Poland.
⁵ Department of Gynecologic Oncology, Institute of Oncology, Warsaw, Poland.
⁶ Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
⁷ University of California at Los Angeles, David Geffen School of Medicine, Department of Medicine, Division of Hematology and Oncology, Los Angeles, CA, USA; University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Universitaetsstrasse 21-23, 91054 Erlangen, Germany.
⁸ University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Universitaetsstrasse 21-23, 91054 Erlangen, Germany.
⁹ University Hospital Erlangen, Institute of Human Genetics, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
¹⁰ Division of Gynecological Oncology, Department of Oncology, University Hospitals Leuven, Belgium.
¹¹ Vesalius Research Center, VIB, Leuven, Belgium; Laboratory for Translational Genetics, Vesalius Research Center, VIB and KU Leuven, Belgium.
¹² Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹³ German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany.
¹⁴ Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany.
¹⁵ Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
¹⁶ Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
¹⁷ Cancer Epidemiology Program, University of Hawaii Cancer Center, HI, USA.
¹⁸ Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹⁹ Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
²⁰ Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
²¹ Department of Gynecology, Jena University Hospital - Friedrich Schiller University, Jena, Germany.
²² Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, HUS, Finland.
²³ Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Ovarian Cancer Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA.
²⁴ Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²⁵ Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany; Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany.
²⁶ Institut für Humangenetik Wiesbaden, Wiesbaden, Germany.
²⁷ Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
²⁸ Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
²⁹ Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
³⁰ Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
³¹ Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
³² Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
³³ Biostatistics and Informatics Shared Resource, University of Kansas Medical Center, Kansas City, KS, USA.
³⁴ Department of Pathology, University of Melbourne, Parkville, VIC Australia.
³⁵ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
³⁶ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.
³⁷ Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³⁸ Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³⁹ College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA.
⁴⁰ Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁴¹ Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA.
⁴² Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA; Cancer Control and Population Sciences, Duke Cancer Institute, Durham, NC, USA.
⁴³ Department of Statistical Science, Duke University, Durham, NC, USA.
⁴⁴ Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
⁴⁵ Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
⁴⁶ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴⁷ Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁴⁸ Cancer Prevention and Control, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
⁴⁹ Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
⁵⁰ Department of Gynaecology, Radboud University Medical Centre, Nijmegen, The Netherlands.
⁵¹ Department for Health Evidence and Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.
⁵² Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands; Comprehensive Cancer Center The Netherlands, Utrecht, The Netherlands.
⁵³ Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Portland, OR, USA.
⁵⁴ Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada.
⁵⁵ Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
⁵⁶ Alberta Health Services-Cancer Care, Department of Population Health Research, Calgary, AB, Canada; Departments of Medical Genetics and Oncology, University of Calgary, Calgary, AB, Canada.
⁵⁷ Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada; Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC Canada.
⁵⁸ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
⁵⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
⁶⁰ Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
⁶¹ Deptartment of Pathology, Rigshospitalet, University of Copenhagen, Denmark.
⁶² Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
⁶³ Department of Pathology, University of Melbourne, Parkville, VIC Australia; Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia.
⁶⁴ Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
⁶⁵ Cancer Research UK Clinical Trials Unit, Glasgow, The Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK.
⁶⁶ Department of Gynaecological Oncology, Glasgow Royal Infirmary, Glasgow, UK.
⁶⁷ Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow, UK.
⁶⁸ Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, CA, USA.
⁶⁹ Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
⁷⁰ Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
⁷¹ Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
⁷² Department of Epidemiology, Genetic Epidemiology Research Institute, School of Medicine, University of California Irvine, Irvine, CA, USA.
⁷³ Department of Epidemiology, University of California Irvine, Irvine, CA, USA.
⁷⁴ Women's Cancer, Institute for Women's Health, University College London, London, UK.
⁷⁵ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁷⁶ Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁷⁷ Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Women's Cancer Research Program, Magee-Women's Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
⁷⁸ Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁷⁹ The University of Texas School of Public Health, Houston, TX, USA.
⁸⁰ Department of Oncology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
⁸¹ 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. Electronic address: lpearce@umich.edu.

PMID: 25528498
PMCID: PMC4892108
DOI: 10.1016/j.ygyno.2014.12.017

Multicenter Study

Evaluating the ovarian cancer gonadotropin hypothesis: a candidate gene study

Alice W Lee et al. Gynecol Oncol. 2015 Mar.

. 2015 Mar;136(3):542-8.

doi: 10.1016/j.ygyno.2014.12.017. Epub 2014 Dec 17.

Authors

Affiliations

¹ Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
² Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
³ Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
⁴ Department of Pathology, Institute of Oncology, Warsaw, Poland.
⁵ Department of Gynecologic Oncology, Institute of Oncology, Warsaw, Poland.
⁶ Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
⁷ University of California at Los Angeles, David Geffen School of Medicine, Department of Medicine, Division of Hematology and Oncology, Los Angeles, CA, USA; University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Universitaetsstrasse 21-23, 91054 Erlangen, Germany.
⁸ University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Universitaetsstrasse 21-23, 91054 Erlangen, Germany.
⁹ University Hospital Erlangen, Institute of Human Genetics, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
¹⁰ Division of Gynecological Oncology, Department of Oncology, University Hospitals Leuven, Belgium.
¹¹ Vesalius Research Center, VIB, Leuven, Belgium; Laboratory for Translational Genetics, Vesalius Research Center, VIB and KU Leuven, Belgium.
¹² Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹³ German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany.
¹⁴ Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany.
¹⁵ Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
¹⁶ Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
¹⁷ Cancer Epidemiology Program, University of Hawaii Cancer Center, HI, USA.
¹⁸ Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹⁹ Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
²⁰ Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
²¹ Department of Gynecology, Jena University Hospital - Friedrich Schiller University, Jena, Germany.
²² Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, HUS, Finland.
²³ Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Ovarian Cancer Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA.
²⁴ Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²⁵ Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany; Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany.
²⁶ Institut für Humangenetik Wiesbaden, Wiesbaden, Germany.
²⁷ Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
²⁸ Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
²⁹ Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
³⁰ Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
³¹ Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
³² Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
³³ Biostatistics and Informatics Shared Resource, University of Kansas Medical Center, Kansas City, KS, USA.
³⁴ Department of Pathology, University of Melbourne, Parkville, VIC Australia.
³⁵ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
³⁶ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.
³⁷ Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³⁸ Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³⁹ College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA.
⁴⁰ Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁴¹ Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA.
⁴² Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA; Cancer Control and Population Sciences, Duke Cancer Institute, Durham, NC, USA.
⁴³ Department of Statistical Science, Duke University, Durham, NC, USA.
⁴⁴ Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
⁴⁵ Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
⁴⁶ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴⁷ Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁴⁸ Cancer Prevention and Control, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
⁴⁹ Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
⁵⁰ Department of Gynaecology, Radboud University Medical Centre, Nijmegen, The Netherlands.
⁵¹ Department for Health Evidence and Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.
⁵² Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands; Comprehensive Cancer Center The Netherlands, Utrecht, The Netherlands.
⁵³ Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Portland, OR, USA.
⁵⁴ Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada.
⁵⁵ Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
⁵⁶ Alberta Health Services-Cancer Care, Department of Population Health Research, Calgary, AB, Canada; Departments of Medical Genetics and Oncology, University of Calgary, Calgary, AB, Canada.
⁵⁷ Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada; Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC Canada.
⁵⁸ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
⁵⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
⁶⁰ Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
⁶¹ Deptartment of Pathology, Rigshospitalet, University of Copenhagen, Denmark.
⁶² Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
⁶³ Department of Pathology, University of Melbourne, Parkville, VIC Australia; Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia.
⁶⁴ Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
⁶⁵ Cancer Research UK Clinical Trials Unit, Glasgow, The Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK.
⁶⁶ Department of Gynaecological Oncology, Glasgow Royal Infirmary, Glasgow, UK.
⁶⁷ Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow, UK.
⁶⁸ Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, CA, USA.
⁶⁹ Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
⁷⁰ Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
⁷¹ Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
⁷² Department of Epidemiology, Genetic Epidemiology Research Institute, School of Medicine, University of California Irvine, Irvine, CA, USA.
⁷³ Department of Epidemiology, University of California Irvine, Irvine, CA, USA.
⁷⁴ Women's Cancer, Institute for Women's Health, University College London, London, UK.
⁷⁵ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁷⁶ Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁷⁷ Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Women's Cancer Research Program, Magee-Women's Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
⁷⁸ Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁷⁹ The University of Texas School of Public Health, Houston, TX, USA.
⁸⁰ Department of Oncology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
⁸¹ 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. Electronic address: lpearce@umich.edu.

PMID: 25528498
PMCID: PMC4892108
DOI: 10.1016/j.ygyno.2014.12.017

Abstract

Objective: Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted.

Methods: Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations.

Results: We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some suggestion of gene-level associations for four gonadotropin signaling pathway genes: INHBB (p=0.045, mucinous), LHCGR (p=0.046, high-grade serous), GNRH (p=0.041, high-grade serous), and FSHB (p=0.036, overall invasive). There was also suggestive evidence for INHA (p=0.060, overall invasive).

Conclusions: Ovarian cancer studies have limited sample numbers, thus fewer genome-wide susceptibility alleles, with only modest associations, have been identified relative to breast and prostate cancers. We have evaluated the majority of ovarian cancer studies with biological samples, to our knowledge, leaving no opportunity for replication. Using both our understanding of biology and powerful gene-level tests, we have identified four putative ovarian cancer loci near INHBB, LHCGR, GNRH, and FSHB that warrant a second look if larger sample sizes and denser genotype chips become available.

Keywords: Gene; Genetic variation; Genetics; Gonadotropins; Ovarian cancer; Polymorphisms.

PubMed Disclaimer

Conflict of interest statement

Andrew Berchuck serves on the PARP inhibitor advisory board for Astra Zeneca and Usha Menon owns shares of Abcodia Ltd., a biomarker validation company.

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Evaluating the ovarian cancer gonadotropin hypothesis: a candidate gene study

Affiliations

Evaluating the ovarian cancer gonadotropin hypothesis: a candidate gene study

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases