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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)
V. Silvestri, G. Leslie, DR. Barnes, CIMBA Group, BA. Agnarsson, K. Aittomäki, E. Alducci, IL. Andrulis, RB. Barkardottir, A. Barroso, D. Barrowdale, J. Benitez, B. Bonanni, A. Borg, SS. Buys, T. Caldés, MA. Caligo, C. Capalbo, I. Campbell, WK....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Grantová podpora
P20 GM130423
NIGMS NIH HHS - United States
- MeSH
- dospělí MeSH
- fenotyp MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory diagnóza genetika MeSH
- protein BRCA1 genetika MeSH
- protein BRCA2 genetika MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- zárodečné mutace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
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.
Area of Clinical and Molecular Genetics University Hospital of Vall d'Hebron Barcelona Spain
Biomedical Sciences Institute University of Porto Porto Portugal
BMC Faculty of Medicine University of Iceland Reykjavik Iceland
Breast Cancer Research Center Genetics Department Motamed Cancer Institute ACECR Tehran Iran
Cancer Epidemiology Division Cancer Council Victoria Melbourne Victoria Australia
Cancer Genetics Service National Cancer Centre Singapore Singapore
Cancer Research Institute Seoul National University Seoul Korea
Cancer Research Malaysia Subang Jaya Selangor Malaysia
Center for Clinical Cancer Genetics The University of Chicago Chicago Illinois
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 Medical Genetics NorthShore University HealthSystem Evanston Illinois
Center for Molecular Medicine Cologne University of Cologne Cologne Germany
Centre for Medical Genetics Ghent University Gent Belgium
Centro de Investigación en Red de Enfermedades Raras Spain
Clinical Cancer Genetics City of Hope Duarte California
Clinical Genetics Karolinska Institutet Stockholm Sweden
Comprehensive Cancer Center Department of OB GYN Medical University of Vienna Vienna Austria
Dana Farber Cancer Institute Boston Massachusetts
Department of Biomedical Sciences Seoul National University Graduate School Seoul Korea
Department of Cancer Biology and Genetics The Ohio State University Columbus
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Clinical Genetics Aarhus University Hospital Aarhus Denmark
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 Odense Denmark
Department of Clinical Genetics Rigshospitalet Copenhagen Denmark
Department of Clinical Genetics Vejle Hospital Vejle Denmark
Department of Clinical Pathology The University of Melbourne Melbourne Victoria Australia
Department of Epidemiology Mailman School of Public Health Columbia University New York New York
Department of Experimental and Clinical Biomedical Sciences University of Florence Florence Italy
Department of Genetics Portuguese Oncology Institute Porto Portugal
Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Ontario Canada
Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota
Department of Medical Oncology Beth Israel Deaconess Medical Center Boston Massachusetts
Department of Molecular Genetics National Institute of Oncology Budapest Hungary
Department of Molecular Genetics University of Toronto Toronto Ontario Canada
Department of Molecular Medicine Sapienza University of Rome Rome Italy
Department of OB GYN Medical University of Vienna Vienna Austria
Department of Oncology and Haematology University of Modena and Reggio Emilia Modena Italy
Department of Oncology Lund University Skåne University Hospital Lund Sweden
Department of Oncology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark
Department of Pathology and Laboratory Medicine University of Kansas Medical Center Kansas City
Department of Pathology Landspitali University Hospital Reykjavik Iceland
Department of Population Sciences Beckman Research Institute of City of Hope Duarte California
Department of Preventive Medicine Seoul National University College of Medicine Seoul Korea
Department of Surgery University of Hong Kong Pok Fu Lam Hong Kong
Department of Tumour Biology INSERM U830 Paris France
Departments of Pediatrics and Medicine Columbia University New York New York
Division of Cancer Prevention and Genetics IEO European Institute of Oncology IRCCS Milan Italy
Family Cancer Clinic Netherlands Cancer Institute Amsterdam the Netherlands
Fundación Pública Galega Medicina Xenómica SERGAS Santiago de Compostela Spain
Genetic Epidemiology of Cancer Team Inserm U900 Paris France
Harvard T H Chan School of Public Health Boston Massachusetts
Hereditary Cancer Genetics Group Vall d'Hebron Institute of Oncology Barcelona Spain
Hong Kong Hereditary Breast Cancer Family Registry Cancer Genetics Centre Happy Valley Hong Kong
Huntsman Cancer Institute Department of Internal Medicine University of Utah Health Salt Lake City
Immunology and Molecular Oncology Unit Veneto Institute of Oncology IOV IRCCS Padua Italy
Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany
Instituto de Investigación Sanitaria de Santiago de Compostela Santiago de Compostela Spain
Laboratory Medicine Program University Health Network Toronto Ontario Canada
Latvian Biomedical Research and Study Centre Riga Latvia
Lee Kong Chian School of Medicine Nanyang Technological University Singapore
Lombardi Comprehensive Cancer Center Georgetown University Washington DC
Magee Womens Hospital University of Pittsburgh School of Medicine Pittsburgh Pennsylvania
Medical Oncology Center National Institute of Oncology Budapest Hungary
Mines ParisTech Fontainebleau France
Molecular Genetics of Breast Cancer German Cancer Research Center Heidelberg Germany
Parkville Familial Cancer Centre Peter MacCallum Cancer Centre Melbourne Victoria Australia
ProCURE Catalan Institute of Oncology IDIBELL Barcelona Spain
Sackler Faculty of Medicine Tel Aviv University Ramat Aviv Israel
School of Medicine University of Iceland Reykjavik Iceland
Service de Génétique Institut Curie Paris France
Sir Peter MacCallum Department of Oncology The University of Melbourne Melbourne Victoria Australia
Spanish Network on Rare Diseases Madrid Spain
The Suzanne Levy Gertner Oncogenetics Unit Chaim Sheba Medical Center Ramat Gan Israel
The University of Chicago Pritzker School of Medicine Chicago Illinois
Université de Paris Paris France
UO Oncologia Medica Azienda Ospedaliero Universitaria Pisana Pisa Italy
Citace poskytuje Crossref.org
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- $a 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) / $c V. Silvestri, G. Leslie, DR. Barnes, CIMBA Group, BA. Agnarsson, K. Aittomäki, E. Alducci, IL. Andrulis, RB. Barkardottir, A. Barroso, D. Barrowdale, J. Benitez, B. Bonanni, A. Borg, SS. Buys, T. Caldés, MA. Caligo, C. Capalbo, I. Campbell, WK. Chung, KBM. Claes, SV. Colonna, L. Cortesi, FJ. Couch, M. de la Hoya, O. Diez, YC. Ding, S. Domchek, DF. Easton, B. Ejlertsen, C. Engel, DG. Evans, L. Feliubadalò, L. Foretova, F. Fostira, L. Géczi, AM. Gerdes, G. Glendon, AK. Godwin, DE. Goldgar, E. Hahnen, FBL. Hogervorst, JL. Hopper, PJ. Hulick, C. Isaacs, A. Izquierdo, PA. James, R. Janavicius, UB. Jensen, EM. John, V. Joseph, I. Konstantopoulou, AW. Kurian, A. Kwong, E. Landucci, F. Lesueur, JT. Loud, E. Machackova, PL. Mai, K. Majidzadeh-A, S. Manoukian, M. Montagna, L. Moserle, AM. Mulligan, KL. Nathanson, H. Nevanlinna, J. Ngeow, L. Nikitina-Zake, K. Offit, E. Olah, OI. Olopade, A. Osorio, L. Papi, SK. Park, IS. Pedersen, P. Perez-Segura, AH. Petersen, P. Pinto, B. Porfirio, MA. Pujana, P. Radice, J. Rantala, MU. Rashid, B. Rosenzweig, M. Rossing, M. Santamariña, RK. Schmutzler, L. Senter, J. Simard, CF. Singer, AR. Solano, MC. Southey, L. Steele, Z. Steinsnyder, D. Stoppa-Lyonnet, YY. Tan, MR. Teixeira, SH. Teo, MB. Terry, M. Thomassen, AE. Toland, S. Torres-Esquius, N. Tung, CJ. van Asperen, A. Vega, A. Viel, J. Vierstraete, B. Wappenschmidt, JN. Weitzel, G. Wieme, SY. Yoon, KK. Zorn, L. McGuffog, MT. Parsons, U. Hamann, MH. Greene, JA. Kirk, SL. Neuhausen, TR. Rebbeck, M. Tischkowitz, G. Chenevix-Trench, AC. Antoniou, E. Friedman, L. Ottini
- 520 9_
- $a 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.
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