Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Frank Qian¹, Matti A Rookus², Goska Leslie³, Harvey A Risch⁴, Mark H Greene⁵, Cora M Aalfs⁶, Muriel A Adank⁷, Julian Adlard⁸, Bjarni A Agnarsson^{9

10}, Munaza Ahmed¹¹, Kristiina Aittomäki¹², Irene L Andrulis^{13

14}, Norbert Arnold^{15

16}, Banu K Arun¹⁷, Margreet G E M Ausems¹⁸, Jacopo Azzollini¹⁹, Daniel Barrowdale³, Julian Barwell²⁰, Javier Benitez^{21

22}, Katarzyna Białkowska²³, Valérie Bonadona²⁴, Julika Borde^{25

26

27}, Ake Borg²⁸, Angela R Bradbury²⁹, Joan Brunet³⁰, Saundra S Buys³¹, Trinidad Caldés³², Maria A Caligo³³, Ian Campbell^{34

35}, Jonathan Carter³⁶, Jocelyne Chiquette³⁷, Wendy K Chung³⁸, Kathleen B M Claes³⁹, J Margriet Collée⁴⁰, Marie-Agnès Collonge-Rame⁴¹, Fergus J Couch⁴², Mary B Daly⁴³, Capucine Delnatte⁴⁴, Orland Diez⁴⁵, Susan M Domchek²⁹, Cecilia M Dorfling⁴⁶, Jacqueline Eason⁴⁷, Douglas F Easton^{3

48}, Ros Eeles⁴⁹, Christoph Engel⁵⁰, D Gareth Evans^{51

52}, Laurence Faivre^{53

54}, Lidia Feliubadaló⁵⁵, Lenka Foretova⁵⁶, Eitan Friedman^{57

58}, Debra Frost³, Patricia A Ganz⁵⁹, Judy Garber⁶⁰, Vanesa Garcia-Barberan³¹, Andrea Gehrig⁶¹, Gord Glendon¹³, Andrew K Godwin⁶², Encarna B Gómez Garcia⁶³, Ute Hamann⁶⁴, Jan Hauke^{24

25

26}, John L Hopper⁶⁵, Peter J Hulick^{66

67}, Evgeny N Imyanitov⁶⁸, Claudine Isaacs⁶⁹, Louise Izatt⁷⁰, Anna Jakubowska^{22

71}, Ramunas Janavicius^{72

73}, Esther M John⁷⁴, Beth Y Karlan⁷⁵, Carolien M Kets⁷⁶, Yael Laitman⁵⁷, Conxi Lázaro⁵⁵, Dominique Leroux⁷⁷, Jenny Lester⁷⁵, Fabienne Lesueur^{78

79}, Jennifer T Loud⁵, Jan Lubiński²³, Alicja Łukomska²³, Lesley McGuffog³, Noura Mebirouk^{78

79

80}, Hanne E J Meijers-Heijboer⁸¹, Alfons Meindl⁸², Austin Miller⁸³, Marco Montagna⁸⁴, Thea M Mooij², Emmanuelle Mouret-Fourme⁸⁵, Katherine L Nathanson²⁹, Bita Nehoray⁸⁶, Susan L Neuhausen⁸⁷, Heli Nevanlinna⁸⁸, Finn C Nielsen⁸⁹, Kenneth Offit^{90

91}, Edith Olah⁹², Kai-Ren Ong⁹³, Jan C Oosterwijk⁹⁴, Laura Ottini⁹⁵, Michael T Parsons⁹⁶, Paolo Peterlongo⁹⁷, Georg Pfeiler⁹⁸, Nisha Pradhan⁹⁰, Paolo Radice⁹⁹, Susan J Ramus^{100

101}, Johanna Rantala¹⁰², Gad Rennert¹⁰³, Mark Robson⁹¹, Gustavo C Rodriguez¹⁰⁴, Ritu Salani¹⁰⁵, Maren T Scheuner¹⁰⁶, Rita K Schmutzler^{26

27}, Payal D Shah²⁹, Lucy E Side¹⁰⁷, Jacques Simard¹⁰⁸, Christian F Singer⁹⁸, Doris Steinemann¹⁰⁹, Dominique Stoppa-Lyonnet^{85

110

111}, Yen Yen Tan⁹⁸, Manuel R Teixeira^{112

113}, Mary Beth Terry¹¹⁴, Mads Thomassen¹¹⁵, Marc Tischkowitz^{116

117}, Silvia Tognazzo⁸⁴, Amanda E Toland¹¹⁸, Nadine Tung¹¹⁹, Christi J van Asperen¹²⁰, Klaartje van Engelen¹²¹, Elizabeth J van Rensburg⁴⁶, Laurence Venat-Bouvet¹²², Jeroen Vierstraete³⁹, Gabriel Wagner⁹⁸, Lisa Walker¹²³, Jeffrey N Weitzel⁸⁶, Drakoulis Yannoukakos¹²⁴; KConFab Investigators; HEBON Investigators; GEMO Study Collaborators; EMBRACE Collaborators; Antonis C Antoniou³, David E Goldgar¹²⁵, Olufunmilayo I Olopade¹²⁶, Georgia Chenevix-Trench⁹⁶, Timothy R Rebbeck^{127

128}, Dezheng Huo^{129

130}; CIMBA

Affiliations

¹ Department of Medicine, University of Chicago, Chicago, IL, USA.
² Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
³ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁴ Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
⁵ Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
⁶ Department of Clinical Genetics, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.
⁷ Family Cancer Clinic, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
⁸ Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK.
⁹ Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.
¹⁰ School of Medicine, University of Iceland, Reykjavik, Iceland.
¹¹ North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK.
¹² Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
¹³ Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
¹⁴ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
¹⁵ Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany.
¹⁶ Institute of Clinical Molecular Biology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany.
¹⁷ Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁸ Division Laboratories, Pharmacy and Biomedical Genetics, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁹ Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
²⁰ Leicestershire Clinical Genetics Service, University Hospitals of Leicester NHS Trust, Leicester, UK.
²¹ Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
²² Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
²³ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
²⁴ Unité de Prévention et d'Epidémiologie Génétique, Centre Léon Bérard, Lyon, France.
²⁵ Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany.
²⁶ Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
²⁷ Center for Hereditary Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany.
²⁸ Department of Oncology, Lund University and Skåne University Hospital, Lund, Sweden.
²⁹ Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
³⁰ Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona), Catalan Institute of Oncology, CIBERONC, Girona, Spain.
³¹ Department of Medicine, Huntsman Cancer Institute, Salt Lake City, UT, USA.
³² Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
³³ Section of Molecular Genetics, Dept. of Laboratory Medicine, University Hospital of Pisa, Pisa, Italy.
³⁴ Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
³⁵ Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
³⁶ Department of Gynaecological Oncology, Chris O'Brien Lifehouse and The University of Sydney, Camperdown, NSW, Australia.
³⁷ CRCHU de Québec- oncologie, Centre des maladies du sein Deschênes-Fabia, Hôpital du Saint-Sacrement, Québec, QC, Canada.
³⁸ Departments of Pediatrics and Medicine, Columbia University, New York, NY, USA.
³⁹ Centre for Medical Genetics, Ghent University, Gent, Belgium.
⁴⁰ Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁴¹ Service de Génétique, CHU de Besançon, Besançon, France.
⁴² Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
⁴³ Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
⁴⁴ Unité d'Oncogénétique, ICO-Centre René Gauducheau, Saint Herblain, France.
⁴⁵ Oncogenetics Group, Clinical and Molecular Genetics Area, Vall d'Hebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron, Barcelona, Spain.
⁴⁶ Department of Genetics, University of Pretoria, Arcadia, South Africa.
⁴⁷ Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, UK.
⁴⁸ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁴⁹ Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK.
⁵⁰ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
⁵¹ Division of Evolution and Genomic Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
⁵² Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
⁵³ Unité d'oncogénétique, Centre de Lutte Contre le Cancer, Centre Georges-François Leclerc, Dijon, France.
⁵⁴ Centre de Génétique, CHU Dijon, Dijon, France.
⁵⁵ Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Bellvitge Biomedical Research Institute, Catalan Institute of Oncology), CIBERONC, Barcelona, Spain.
⁵⁶ Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
⁵⁷ The Susanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, Ramat Gan, Israel.
⁵⁸ Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
⁵⁹ Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Centre, UCLA, Los Angeles, CA, USA.
⁶⁰ Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, MA, USA.
⁶¹ Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics, University Würzburg, Würzburg, Germany.
⁶² Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, KS, USA.
⁶³ Department of Clinical Genetics and GROW, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
⁶⁴ Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶⁵ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
⁶⁶ Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL, USA.
⁶⁷ The University of Chicago Pritzker School of Medicine, Chicago, IL, USA.
⁶⁸ N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
⁶⁹ Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
⁷⁰ Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁷¹ Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland.
⁷² Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.
⁷³ State Research Institute, Innovative Medicine Center, Vilnius, CA, Lithuania.
⁷⁴ Department of Medicine, Division of Oncology, and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
⁷⁵ Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁷⁶ Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
⁷⁷ Département de Génétique, CHU de Grenoble, Grenoble, France.
⁷⁸ Genetic Epidemiology of Cancer team, Inserm U900, Paris, France.
⁷⁹ Institut Curie, Paris, France.
⁸⁰ Mines ParisTech, Fontainebleau, France.
⁸¹ Department of Clinical Genetics, Amsterdam UMC, Location VU University Medical Center, Amsterdam, The Netherlands.
⁸² Department of Gynecology and Obstetrics, Ludwig Maximilian University of Munich, Munich, Germany.
⁸³ NRG Oncology, Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, NY, USA.
⁸⁴ Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.
⁸⁵ Service de Génétique, Institut Curie, Paris, France.
⁸⁶ Clinical Cancer Genomics, City of Hope, Duarte, CA, USA.
⁸⁷ Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
⁸⁸ Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
⁸⁹ Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
⁹⁰ Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
⁹¹ Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
⁹² Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.
⁹³ West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Birmingham, UK.
⁹⁴ Department of Genetics, University Medical Center Groningen, University Groningen, Groningen, The Netherlands.
⁹⁵ Department of Molecular Medicine, University La Sapienza, Rome, Italy.
⁹⁶ Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
⁹⁷ Genome Diagnostics Program, IFOM - the FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy.
⁹⁸ Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
⁹⁹ Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
¹⁰⁰ School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, NSW, Australia.
¹⁰¹ The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia.
¹⁰² Clinical Genetics, Karolinska Institutet, Stockholm, Sweden.
¹⁰³ Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.
¹⁰⁴ Division of Gynecologic Oncology, NorthShore University HealthSystem, University of Chicago, Evanston, IL, USA.
¹⁰⁵ Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
¹⁰⁶ Cancer Genetics and Prevention Program, University of California San Francisco, San Francisco, CA, USA.
¹⁰⁷ Wessex Clinical Genetics Service, University Hospitals Southampton NHS Trust, Southampton, UK.
¹⁰⁸ Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval, Research Center, Québec City, QC, Canada.
¹⁰⁹ Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany.
¹¹⁰ Department of Tumour Biology, INSERM U830, Paris, France.
¹¹¹ Université Paris Descartes, Paris, France.
¹¹² Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
¹¹³ Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.
¹¹⁴ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹¹⁵ Department of Clinical Genetics, Odense University Hospital, Odence C, Denmark.
¹¹⁶ Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montréal, QC, Canada.
¹¹⁷ Department of Medical Genetics, University of Cambridge, Cambridge, UK.
¹¹⁸ Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
¹¹⁹ Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹²⁰ Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
¹²¹ Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
¹²² Department of Medical Oncology, CHU Dupuytren, Limoges, France.
¹²³ Oxford Regional Genetics Service, Churchill Hospital, Oxford, UK.
¹²⁴ Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens, Greece.
¹²⁵ Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
¹²⁶ Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL, USA.
¹²⁷ Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹²⁸ Dana-Farber Cancer Institute, Boston, MA, USA.
¹²⁹ Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL, USA. dhuo@health.bsd.uchicago.edu.
¹³⁰ Department of Public Health Sciences, University of Chicago, Chicago, IL, USA. dhuo@health.bsd.uchicago.edu.

PMID: 31213659
PMCID: PMC6738050
DOI: 10.1038/s41416-019-0492-8

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Frank Qian et al. Br J Cancer. 2019 Jul.

. 2019 Jul;121(2):180-192.

doi: 10.1038/s41416-019-0492-8. Epub 2019 Jun 19.

Authors

Affiliations

¹ Department of Medicine, University of Chicago, Chicago, IL, USA.
² Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
³ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁴ Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
⁵ Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
⁶ Department of Clinical Genetics, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.
⁷ Family Cancer Clinic, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
⁸ Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK.
⁹ Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.
¹⁰ School of Medicine, University of Iceland, Reykjavik, Iceland.
¹¹ North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK.
¹² Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
¹³ Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
¹⁴ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
¹⁵ Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany.
¹⁶ Institute of Clinical Molecular Biology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany.
¹⁷ Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁸ Division Laboratories, Pharmacy and Biomedical Genetics, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁹ Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
²⁰ Leicestershire Clinical Genetics Service, University Hospitals of Leicester NHS Trust, Leicester, UK.
²¹ Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
²² Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
²³ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
²⁴ Unité de Prévention et d'Epidémiologie Génétique, Centre Léon Bérard, Lyon, France.
²⁵ Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany.
²⁶ Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
²⁷ Center for Hereditary Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany.
²⁸ Department of Oncology, Lund University and Skåne University Hospital, Lund, Sweden.
²⁹ Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
³⁰ Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona), Catalan Institute of Oncology, CIBERONC, Girona, Spain.
³¹ Department of Medicine, Huntsman Cancer Institute, Salt Lake City, UT, USA.
³² Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
³³ Section of Molecular Genetics, Dept. of Laboratory Medicine, University Hospital of Pisa, Pisa, Italy.
³⁴ Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
³⁵ Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
³⁶ Department of Gynaecological Oncology, Chris O'Brien Lifehouse and The University of Sydney, Camperdown, NSW, Australia.
³⁷ CRCHU de Québec- oncologie, Centre des maladies du sein Deschênes-Fabia, Hôpital du Saint-Sacrement, Québec, QC, Canada.
³⁸ Departments of Pediatrics and Medicine, Columbia University, New York, NY, USA.
³⁹ Centre for Medical Genetics, Ghent University, Gent, Belgium.
⁴⁰ Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁴¹ Service de Génétique, CHU de Besançon, Besançon, France.
⁴² Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
⁴³ Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
⁴⁴ Unité d'Oncogénétique, ICO-Centre René Gauducheau, Saint Herblain, France.
⁴⁵ Oncogenetics Group, Clinical and Molecular Genetics Area, Vall d'Hebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron, Barcelona, Spain.
⁴⁶ Department of Genetics, University of Pretoria, Arcadia, South Africa.
⁴⁷ Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, UK.
⁴⁸ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁴⁹ Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK.
⁵⁰ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
⁵¹ Division of Evolution and Genomic Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
⁵² Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
⁵³ Unité d'oncogénétique, Centre de Lutte Contre le Cancer, Centre Georges-François Leclerc, Dijon, France.
⁵⁴ Centre de Génétique, CHU Dijon, Dijon, France.
⁵⁵ Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Bellvitge Biomedical Research Institute, Catalan Institute of Oncology), CIBERONC, Barcelona, Spain.
⁵⁶ Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
⁵⁷ The Susanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, Ramat Gan, Israel.
⁵⁸ Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
⁵⁹ Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Centre, UCLA, Los Angeles, CA, USA.
⁶⁰ Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, MA, USA.
⁶¹ Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics, University Würzburg, Würzburg, Germany.
⁶² Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, KS, USA.
⁶³ Department of Clinical Genetics and GROW, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
⁶⁴ Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶⁵ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
⁶⁶ Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL, USA.
⁶⁷ The University of Chicago Pritzker School of Medicine, Chicago, IL, USA.
⁶⁸ N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
⁶⁹ Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
⁷⁰ Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁷¹ Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland.
⁷² Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.
⁷³ State Research Institute, Innovative Medicine Center, Vilnius, CA, Lithuania.
⁷⁴ Department of Medicine, Division of Oncology, and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
⁷⁵ Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁷⁶ Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
⁷⁷ Département de Génétique, CHU de Grenoble, Grenoble, France.
⁷⁸ Genetic Epidemiology of Cancer team, Inserm U900, Paris, France.
⁷⁹ Institut Curie, Paris, France.
⁸⁰ Mines ParisTech, Fontainebleau, France.
⁸¹ Department of Clinical Genetics, Amsterdam UMC, Location VU University Medical Center, Amsterdam, The Netherlands.
⁸² Department of Gynecology and Obstetrics, Ludwig Maximilian University of Munich, Munich, Germany.
⁸³ NRG Oncology, Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, NY, USA.
⁸⁴ Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.
⁸⁵ Service de Génétique, Institut Curie, Paris, France.
⁸⁶ Clinical Cancer Genomics, City of Hope, Duarte, CA, USA.
⁸⁷ Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
⁸⁸ Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
⁸⁹ Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
⁹⁰ Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
⁹¹ Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
⁹² Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.
⁹³ West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Birmingham, UK.
⁹⁴ Department of Genetics, University Medical Center Groningen, University Groningen, Groningen, The Netherlands.
⁹⁵ Department of Molecular Medicine, University La Sapienza, Rome, Italy.
⁹⁶ Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
⁹⁷ Genome Diagnostics Program, IFOM - the FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy.
⁹⁸ Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
⁹⁹ Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
¹⁰⁰ School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, NSW, Australia.
¹⁰¹ The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia.
¹⁰² Clinical Genetics, Karolinska Institutet, Stockholm, Sweden.
¹⁰³ Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.
¹⁰⁴ Division of Gynecologic Oncology, NorthShore University HealthSystem, University of Chicago, Evanston, IL, USA.
¹⁰⁵ Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
¹⁰⁶ Cancer Genetics and Prevention Program, University of California San Francisco, San Francisco, CA, USA.
¹⁰⁷ Wessex Clinical Genetics Service, University Hospitals Southampton NHS Trust, Southampton, UK.
¹⁰⁸ Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval, Research Center, Québec City, QC, Canada.
¹⁰⁹ Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany.
¹¹⁰ Department of Tumour Biology, INSERM U830, Paris, France.
¹¹¹ Université Paris Descartes, Paris, France.
¹¹² Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
¹¹³ Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.
¹¹⁴ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹¹⁵ Department of Clinical Genetics, Odense University Hospital, Odence C, Denmark.
¹¹⁶ Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montréal, QC, Canada.
¹¹⁷ Department of Medical Genetics, University of Cambridge, Cambridge, UK.
¹¹⁸ Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
¹¹⁹ Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹²⁰ Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
¹²¹ Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
¹²² Department of Medical Oncology, CHU Dupuytren, Limoges, France.
¹²³ Oxford Regional Genetics Service, Churchill Hospital, Oxford, UK.
¹²⁴ Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens, Greece.
¹²⁵ Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
¹²⁶ Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL, USA.
¹²⁷ Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹²⁸ Dana-Farber Cancer Institute, Boston, MA, USA.
¹²⁹ Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL, USA. dhuo@health.bsd.uchicago.edu.
¹³⁰ Department of Public Health Sciences, University of Chicago, Chicago, IL, USA. dhuo@health.bsd.uchicago.edu.

PMID: 31213659
PMCID: PMC6738050
DOI: 10.1038/s41416-019-0492-8

Abstract

Background: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown.

Methods: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models.

Results: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m² increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (P_interaction < 0.05).

Conclusion: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.

PubMed Disclaimer

Conflict of interest statement

G.P. received honoraria and grant from Pfizer, Roche, Novartis, Accord, AstraZeneca, Amgen, Accord and Lilly. R.S. served on advisory board for Tesaro, Clovis, Astra Zeneca, Ethicon and Genmab, and speaker’s bureau for Tesaro and Genentech. The other authors declare no competing interests.

References

1. Salehi F, Dunfield L, Phillips KP, Krewski D, Vanderhyden BC. Risk factors for ovarian cancer: an overview with emphasis on hormonal factors. J. Toxicol. Environ. Health B Crit. Rev. 2008;11:301–321. doi: 10.1080/10937400701876095. - DOI - PubMed
1. Wentzensen N, Poole EM, Trabert B, White E, Arslan AA, Patel AV, et al. Ovarian cancer risk factors by histologic subtype: an analysis from the Ovarian Cancer Cohort Consortium. J. Clin. Oncol. 2016;34:2888–2898. doi: 10.1200/JCO.2016.66.8178. - DOI - PMC - PubMed
1. Rauh-Hain JA, Krivak TC, Del Carmen MG, Olawaiye AB. Ovarian cancer screening and early detection in the general population. Rev. Obstet. Gynecol. 2011;4:15–21. - PMC - PubMed
1. Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi JK, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2016;387:945–956. doi: 10.1016/S0140-6736(15)01224-6. - DOI - PMC - PubMed
1. Neff RT, Senter L, Salani R. BRCA mutation in ovarian cancer: testing, implications and treatment considerations. Ther. Adv. Med. Oncol. 2017;9:519–531. doi: 10.1177/1758834017714993. - DOI - PMC - PubMed

Publication types

Actions
Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information
Molecular Biology Databases
- NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Affiliations

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases

Miscellaneous