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Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.
Qian, Frank; Rookus, Matti A; Leslie, Goska; Risch, Harvey A; Greene, Mark H; Aalfs, Cora M; Adank, Muriel A; Adlard, Julian; Agnarsson, Bjarni A; Ahmed, Munaza; Aittomäki, Kristiina; Andrulis, Irene L; Arnold, Norbert; Arun, Banu K; Ausems, Margreet G E M; Azzollini, Jacopo; Barrowdale, Daniel; Barwell, Julian; Benitez, Javier; Bialkowska, Katarzyna; Bonadona, Valérie; Borde, Julika; Borg, Ake; Bradbury, Angela R; Brunet, Joan; Buys, Saundra S; Caldés, Trinidad; Caligo, Maria A; Campbell, Ian; Carter, Jonathan; Chiquette, Jocelyne; Chung, Wendy K; Claes, Kathleen B M; Collée, J Margriet; Collonge-Rame, Marie-Agnès; Couch, Fergus J; Daly, Mary B; Delnatte, Capucine; Diez, Orland; Domchek, Susan M; Dorfling, Cecilia M; Eason, Jacqueline; Easton, Douglas F; Eeles, Ros; Engel, Christoph; Evans, D Gareth; Faivre, Laurence; Feliubadaló, Lidia; Foretova, Lenka; Friedman, Eitan.
Afiliação
  • Qian F; Department of Medicine, University of Chicago, Chicago, IL, USA.
  • Rookus MA; Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Leslie G; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Risch HA; Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
  • Greene MH; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Aalfs CM; Department of Clinical Genetics, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.
  • Adank MA; Family Cancer Clinic, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
  • Adlard J; Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK.
  • Agnarsson BA; Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.
  • Ahmed M; School of Medicine, University of Iceland, Reykjavik, Iceland.
  • Aittomäki K; North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK.
  • Andrulis IL; Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
  • Arnold N; Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
  • Arun BK; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
  • Ausems MGEM; Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany.
  • Azzollini J; Institute of Clinical Molecular Biology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany.
  • Barrowdale D; Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Barwell J; Division Laboratories, Pharmacy and Biomedical Genetics, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Benitez J; Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  • Bialkowska K; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Bonadona V; Leicestershire Clinical Genetics Service, University Hospitals of Leicester NHS Trust, Leicester, UK.
  • Borde J; Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
  • Borg A; Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
  • Bradbury AR; Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
  • Brunet J; Unité de Prévention et d'Epidémiologie Génétique, Centre Léon Bérard, Lyon, France.
  • Buys SS; Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany.
  • Caldés T; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
  • Caligo MA; Center for Hereditary Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany.
  • Campbell I; Department of Oncology, Lund University and Skåne University Hospital, Lund, Sweden.
  • Carter J; Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  • Chiquette J; Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona), Catalan Institute of Oncology, CIBERONC, Girona, Spain.
  • Chung WK; Department of Medicine, Huntsman Cancer Institute, Salt Lake City, UT, USA.
  • Claes KBM; Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
  • Collée JM; Section of Molecular Genetics, Dept. of Laboratory Medicine, University Hospital of Pisa, Pisa, Italy.
  • Collonge-Rame MA; Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
  • Couch FJ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
  • Daly MB; Department of Gynaecological Oncology, Chris O'Brien Lifehouse and The University of Sydney, Camperdown, NSW, Australia.
  • Delnatte C; CRCHU de Québec- oncologie, Centre des maladies du sein Deschênes-Fabia, Hôpital du Saint-Sacrement, Québec, QC, Canada.
  • Diez O; Departments of Pediatrics and Medicine, Columbia University, New York, NY, USA.
  • Domchek SM; Centre for Medical Genetics, Ghent University, Gent, Belgium.
  • Dorfling CM; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Eason J; Service de Génétique, CHU de Besançon, Besançon, France.
  • Easton DF; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Eeles R; Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
  • Engel C; Unité d'Oncogénétique, ICO-Centre René Gauducheau, Saint Herblain, France.
  • Evans DG; Oncogenetics Group, Clinical and Molecular Genetics Area, Vall d'Hebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron, Barcelona, Spain.
  • Faivre L; Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  • Feliubadaló L; Department of Genetics, University of Pretoria, Arcadia, South Africa.
  • Foretova L; Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, UK.
  • Friedman E; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Br J Cancer ; 121(2): 180-192, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31213659
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 (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.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Estatura / Índice de Massa Corporal / Genes BRCA1 / Genes BRCA2 / Análise da Randomização Mendeliana / Heterozigoto / Mutação Limite: Adulto / Idoso / Feminino / Humanos / Meia-Idade Idioma: Inglês Revista: Br J Cancer Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Estados Unidos

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Estatura / Índice de Massa Corporal / Genes BRCA1 / Genes BRCA2 / Análise da Randomização Mendeliana / Heterozigoto / Mutação Limite: Adulto / Idoso / Feminino / Humanos / Meia-Idade Idioma: Inglês Revista: Br J Cancer Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Estados Unidos