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 (Pinteraction < 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.

Biomedical Network on Rare Diseases Madrid Spain

Biomedical Sciences Institute University of Porto Porto Portugal

Cancer Genetics and Prevention Program University of California San Francisco San Francisco CA USA

Cancer Risk and Prevention Clinic Dana Farber Cancer Institute Boston MA USA

Center for Clinical Cancer Genetics The University of Chicago Chicago IL USA

Center for Genomic Medicine Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Center for Hereditary Breast and Ovarian Cancer University Hospital of Cologne Cologne Germany

Center for Integrated Oncology University Hospital of Cologne Cologne Germany

Center for Medical Genetics NorthShore University HealthSystem Evanston IL USA

Center for Molecular Medicine Cologne University of Cologne Cologne Germany

Centre de Génétique CHU Dijon Dijon France

Centre for Cancer Genetic Epidemiology Department of Oncology University of Cambridge Cambridge UK

Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care University of Cambridge Cambridge UK

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne Melbourne VIC Australia

Centre for Medical Genetics Ghent University Gent Belgium

Centre of Familial Breast and Ovarian Cancer Department of Medical Genetics Institute of Human Genetics University Würzburg Würzburg Germany

Chronic Disease Epidemiology Yale School of Public Health New Haven CT USA

Clalit National Cancer Control Center Carmel Medical Center and Technion Faculty of Medicine Haifa Israel

Clinical Cancer Genomics City of Hope Duarte CA USA

Clinical Genetics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD USA

Clinical Genetics Guy's and St Thomas' NHS Foundation Trust London UK

Clinical Genetics Karolinska Institutet Stockholm Sweden

Clinical Genetics Research Lab Department of Cancer Biology and Genetics Memorial Sloan Kettering Cancer Center New York NY USA

Clinical Genetics Service Department of Medicine Memorial Sloan Kettering Cancer Center New York NY USA

CRCHU de Québec oncologie Centre des maladies du sein Deschênes Fabia Hôpital du Saint Sacrement Québec QC Canada

Dana Farber Cancer Institute Boston MA USA

Département de Génétique CHU de Grenoble Grenoble France

Department of Breast Medical Oncology University of Texas MD Anderson Cancer Center Houston TX USA

Department of Cancer Biology and Genetics The Ohio State University Columbus OH USA

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Clinical Genetics Amsterdam UMC Location AMC Amsterdam The Netherlands

Department of Clinical Genetics Amsterdam UMC Location VU University Medical Center Amsterdam The Netherlands

Department of Clinical Genetics Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands

Department of Clinical Genetics and GROW School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht The Netherlands

Department of Clinical Genetics Erasmus University Medical Center Rotterdam The Netherlands

Department of Clinical Genetics Fox Chase Cancer Center Philadelphia PA USA

Department of Clinical Genetics Helsinki University Hospital University of Helsinki Helsinki Finland

Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands

Department of Clinical Genetics Odense University Hospital Odence C Denmark

Department of Dermatology Huntsman Cancer Institute University of Utah School of Medicine Salt Lake City UT USA

Department of Epidemiology Mailman School of Public Health Columbia University New York NY USA

Department of Epidemiology The Netherlands Cancer Institute Amsterdam The Netherlands

Department of Genetics and Computational Biology QIMR Berghofer Medical Research Institute Brisbane QLD Australia

Department of Genetics and Pathology Pomeranian Medical University Szczecin Poland

Department of Genetics Portuguese Oncology Institute Porto Portugal

Department of Genetics University Medical Center Groningen University Groningen Groningen The Netherlands

Department of Genetics University of Pretoria Arcadia South Africa

Department of Gynaecological Oncology Chris O'Brien Lifehouse and The University of Sydney Camperdown NSW Australia

Department of Gynaecology and Obstetrics University Hospital of Schleswig Holstein Campus Kiel Christian Albrechts University Kiel Kiel Germany

Department of Gynecology and Obstetrics Ludwig Maximilian University of Munich Munich Germany

Department of Human Genetics Radboud University Medical Center Nijmegen The Netherlands

Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA

Department of Medical Genetics University of Cambridge Cambridge UK

Department of Medical Oncology Beth Israel Deaconess Medical Center Boston MA USA

Department of Medical Oncology CHU Dupuytren Limoges France

Department of Medicine Abramson Cancer Center Perelman School of Medicine at the University of Pennsylvania Philadelphia PA USA

Department of Medicine Division of Oncology and Stanford Cancer Institute Stanford University School of Medicine Stanford CA USA

Department of Medicine Huntsman Cancer Institute Salt Lake City UT USA

Department of Medicine University of Chicago Chicago IL USA

Department of Molecular Genetics National Institute of Oncology Budapest Hungary

Department of Molecular Genetics University of Toronto Toronto ON Canada

Department of Molecular Medicine University La Sapienza Rome Italy

Department of OB GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Obstetrics and Gynecology Helsinki University Hospital University of Helsinki Helsinki Finland

Department of Oncology Lund University and Skåne University Hospital Lund Sweden

Department of Pathology and Laboratory Medicine Kansas University Medical Center Kansas City KS USA

Department of Pathology Landspitali University Hospital Reykjavik Iceland

Department of Population Sciences Beckman Research Institute of City of Hope Duarte CA USA

Department of Public Health Sciences University of Chicago Chicago IL USA

Department of Tumour Biology INSERM U830 Paris France

Departments of Pediatrics and Medicine Columbia University New York NY USA

Division Laboratories Pharmacy and Biomedical Genetics Department of Medical Genetics University Medical Center Utrecht Utrecht The Netherlands

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

Division of Gynecologic Oncology NorthShore University HealthSystem University of Chicago Evanston IL USA

Family Cancer Clinic The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands

Fred A Litwin Center for Cancer Genetics Lunenfeld Tanenbaum Research Institute of Mount Sinai Hospital Toronto ON Canada

Genetic Counseling Unit Hereditary Cancer Program IDIBGI Catalan Institute of Oncology CIBERONC Girona Spain

Genetic Epidemiology of Cancer team Inserm U900 Paris France

Genome Diagnostics Program IFOM the FIRC Institute of Molecular Oncology Milan Italy

Genomics Center Centre Hospitalier Universitaire de Québec Université Laval Research Center Québec City QC Canada

Harvard T H Chan School of Public Health Boston MA USA

Hematology oncology and transfusion medicine center Dept of Molecular and Regenerative Medicine Vilnius University Hospital Santariskiu Clinics Vilnius Lithuania

Human Cancer Genetics Programme Spanish National Cancer Research Centre Madrid Spain

Immunology and Molecular Oncology Unit Veneto Institute of Oncology IOV IRCCS Padua Italy

Independent Laboratory of Molecular Biology and Genetic Diagnostics Pomeranian Medical University Szczecin Poland

Institut Curie Paris France

Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany

Institute of Cell and Molecular Pathology Hannover Medical School Hannover Germany

Institute of Clinical Molecular Biology University Hospital of Schleswig Holstein Campus Kiel Christian Albrechts University Kiel Kiel Germany

Leicestershire Clinical Genetics Service University Hospitals of Leicester NHS Trust Leicester UK

Lombardi Comprehensive Cancer Center Georgetown University Washington DC USA

Manchester Centre for Genomic Medicine St Mary's Hospital Central Manchester University Hospitals NHS Foundation Trust Manchester Academic Health Science Centre Manchester UK

Medical Oncology Department Hospital Clínico San Carlos Instituto de Investigación Sanitaria San Carlos Madrid Spain

Mines ParisTech Fontainebleau France

Molecular Diagnostic Unit Hereditary Cancer Program ICO IDIBELL CIBERONC Barcelona Spain

Molecular Diagnostics Laboratory INRASTES National Centre for Scientific Research 'Demokritos' Athens Greece

Molecular Genetics of Breast Cancer German Cancer Research Center Heidelberg Germany

N N Petrov Institute of Oncology St Petersburg Russia

North East Thames Regional Genetics Service Great Ormond Street Hospital London UK

Nottingham Clinical Genetics Service Nottingham University Hospitals NHS Trust Nottingham UK

NRG Oncology Statistics and Data Management Center Roswell Park Cancer Institute Buffalo NY USA

Oncogenetics Group Clinical and Molecular Genetics Area Vall d'Hebron Institute of Oncology University Hospital Vall d'Hebron Barcelona Spain

Oncogenetics Team The Institute of Cancer Research and Royal Marsden NHS Foundation Trust London UK

Oxford Regional Genetics Service Churchill Hospital Oxford UK

Peter MacCallum Cancer Center Melbourne Victoria Australia

Program in Cancer Genetics Departments of Human Genetics and Oncology McGill University Montréal QC Canada

Sackler Faculty of Medicine Tel Aviv University Ramat Aviv Israel

School of Medicine University of Iceland Reykjavik Iceland

School of Women's and Children's Health Faculty of Medicine University of NSW Sydney Sydney NSW Australia

Schools of Medicine and Public Health Division of Cancer Prevention and Control Research Jonsson Comprehensive Cancer Centre UCLA Los Angeles CA USA

Section of Molecular Genetics Dept of Laboratory Medicine University Hospital of Pisa Pisa Italy

Service de Génétique CHU de Besançon Besançon France

Service de Génétique Institut Curie Paris France

Sir Peter MacCallum Department of Oncology The University of Melbourne Melbourne VIC Australia

State Research Institute Innovative Medicine Center Vilnius CA Lithuania

The Kinghorn Cancer Centre Garvan Institute of Medical Research Sydney NSW Australia

The Susanne Levy Gertner Oncogenetics Unit Chaim Sheba Medical Center Ramat Gan Israel

The University of Chicago Pritzker School of Medicine Chicago IL USA

Unit of Medical Genetics Department of Medical Oncology and Hematology Fondazione IRCCS Istituto Nazionale dei Tumori di Milano Milan Italy

Unit of Molecular Bases of Genetic Risk and Genetic Testing Department of Research Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy

Unité d'oncogénétique Centre de Lutte Contre le Cancer Centre Georges François Leclerc Dijon France

Unité d'Oncogénétique ICO Centre René Gauducheau Saint Herblain France

Unité de Prévention et d'Epidémiologie Génétique Centre Léon Bérard Lyon France

Université Paris Descartes Paris France

Wessex Clinical Genetics Service University Hospitals Southampton NHS Trust Southampton UK

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Wexner Medical Center The Ohio State University Columbus OH USA

Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute Cedars Sinai Medical Center Los Angeles CA USA

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