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Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).
Silvestri, Valentina; Leslie, Goska; Barnes, Daniel R; Agnarsson, Bjarni A; Aittomäki, Kristiina; Alducci, Elisa; Andrulis, Irene L; Barkardottir, Rosa B; Barroso, Alicia; Barrowdale, Daniel; Benitez, Javier; Bonanni, Bernardo; Borg, Ake; Buys, Saundra S; Caldés, Trinidad; Caligo, Maria A; Capalbo, Carlo; Campbell, Ian; Chung, Wendy K; Claes, Kathleen B M; Colonna, Sarah V; Cortesi, Laura; Couch, Fergus J; de la Hoya, Miguel; Diez, Orland; Ding, Yuan Chun; Domchek, Susan; Easton, Douglas F; Ejlertsen, Bent; Engel, Christoph; Evans, D Gareth; Feliubadalò, Lidia; Foretova, Lenka; Fostira, Florentia; Géczi, Lajos; Gerdes, Anne-Marie; Glendon, Gord; Godwin, Andrew K; Goldgar, David E; Hahnen, Eric; Hogervorst, Frans B L; Hopper, John L; Hulick, Peter J; Isaacs, Claudine; Izquierdo, Angel; James, Paul A; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Joseph, Vijai.
Afiliación
  • Silvestri V; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Leslie G; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Barnes DR; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Agnarsson BA; Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.
  • Aittomäki K; School of Medicine, University of Iceland, Reykjavik, Iceland.
  • Alducci E; Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
  • Andrulis IL; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
  • Barkardottir RB; Lunenfeld-Tanenbaum Research Institute, Fred A. Litwin Center for Cancer Genetics, Mount Sinai Hospital, Toronto, Ontario, Canada.
  • Barroso A; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
  • Barrowdale D; Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.
  • Benitez J; BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Bonanni B; Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid, Spain.
  • Borg A; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Buys SS; Human Genetics Group and Genotyping Unit, CEGEN, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid, Spain.
  • Caldés T; Spanish Network on Rare Diseases (CIBERER), Madrid, Spain.
  • Caligo MA; Division of Cancer Prevention and Genetics-IEO, European Institute of Oncology IRCCS, Milan, Italy.
  • Capalbo C; Department of Oncology, Lund University, Skåne University Hospital, Lund, Sweden.
  • Campbell I; Huntsman Cancer Institute, Department of Internal Medicine, University of Utah Health, Salt Lake City.
  • Chung WK; Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain.
  • Claes KBM; Section of Molecular Genetics, Department of Laboratory Medicine, University Hospital of Pisa, Pisa, Italy.
  • Colonna SV; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Cortesi L; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
  • Couch FJ; Departments of Pediatrics and Medicine, Columbia University, New York, New York.
  • de la Hoya M; Centre for Medical Genetics, Ghent University, Gent, Belgium.
  • Diez O; Huntsman Cancer Institute, Department of Internal Medicine, University of Utah Health, Salt Lake City.
  • Ding YC; Department of Oncology and Haematology, University of Modena and Reggio Emilia, Modena, Italy.
  • Domchek S; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
  • Easton DF; Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain.
  • Ejlertsen B; Hereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
  • Engel C; Area of Clinical and Molecular Genetics, University Hospital of Vall d'Hebron, Barcelona, Spain.
  • Evans DG; Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California.
  • Feliubadalò L; Abramson Cancer Center, Perelman School of Medicine, Department of Medicine, University of Pennsylvania, Philadelphia.
  • Foretova L; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Fostira F; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
  • Géczi L; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Gerdes AM; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
  • Glendon G; Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Science, Manchester University, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.
  • Godwin AK; Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, CIBERONC, Barcelona, Spain.
  • Goldgar DE; Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
  • Hahnen E; Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research "Demokritos", Athens, Greece.
  • Hogervorst FBL; Medical Oncology Center, National Institute of Oncology, Budapest, Hungary.
  • Hopper JL; Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.
  • Hulick PJ; Lunenfeld-Tanenbaum Research Institute, Fred A. Litwin Center for Cancer Genetics, Mount Sinai Hospital, Toronto, Ontario, Canada.
  • Isaacs C; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City.
  • Izquierdo A; Huntsman Cancer Institute, Department of Dermatology, University of Utah School of Medicine, Salt Lake City.
  • James PA; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
  • Janavicius R; Center for Hereditary Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany.
  • Jensen UB; Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • John EM; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Joseph V; Center for Medical Genetics, NorthShore University HealthSystem, Evanston, Illinois.
JAMA Oncol ; 6(8): 1218-1230, 2020 08 01.
Article en En | MEDLINE | ID: mdl-32614418
Importance: The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population. Objective: To compare the cancer spectrum and frequencies between male BRCA1 and BRCA2 PV carriers. Design, Setting, and Participants: Retrospective cohort study of 6902 men, including 3651 BRCA1 and 3251 BRCA2 PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Clinical data and pathologic characteristics were collected. Main Outcomes and Measures: BRCA1/2 status was the outcome in a logistic regression, and cancer diagnoses were the independent predictors. All odds ratios (ORs) were adjusted for age, country of origin, and calendar year of the first interview. Results: Among the 6902 men in the study (median [range] age, 51.6 [18-100] years), 1634 cancers were diagnosed in 1376 men (19.9%), the majority (922 of 1,376 [67%]) being BRCA2 PV carriers. Being affected by any cancer was associated with a higher probability of being a BRCA2, rather than a BRCA1, PV carrier (OR, 3.23; 95% CI, 2.81-3.70; P < .001), as well as developing 2 (OR, 7.97; 95% CI, 5.47-11.60; P < .001) and 3 (OR, 19.60; 95% CI, 4.64-82.89; P < .001) primary tumors. A higher frequency of breast (OR, 5.47; 95% CI, 4.06-7.37; P < .001) and prostate (OR, 1.39; 95% CI, 1.09-1.78; P = .008) cancers was associated with a higher probability of being a BRCA2 PV carrier. Among cancers other than breast and prostate, pancreatic cancer was associated with a higher probability (OR, 3.00; 95% CI, 1.55-5.81; P = .001) and colorectal cancer with a lower probability (OR, 0.47; 95% CI, 0.29-0.78; P = .003) of being a BRCA2 PV carrier. Conclusions and Relevance: Significant differences in the cancer spectrum were observed in male BRCA2, compared with BRCA1, PV carriers. These data may inform future recommendations for surveillance of BRCA1/2-associated cancers and guide future prospective studies for estimating cancer risks in men with BRCA1/2 PVs.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína BRCA1 / Proteína BRCA2 / Neoplasias Tipo de estudio: Diagnostic_studies / Guideline / Observational_studies / Prognostic_studies / Qualitative_research Límite: Adolescent / Adult / Aged / Aged80 / Humans / Male / Middle aged Idioma: En Revista: JAMA Oncol Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína BRCA1 / Proteína BRCA2 / Neoplasias Tipo de estudio: Diagnostic_studies / Guideline / Observational_studies / Prognostic_studies / Qualitative_research Límite: Adolescent / Adult / Aged / Aged80 / Humans / Male / Middle aged Idioma: En Revista: JAMA Oncol Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos