Journal
JAMA ONCOLOGY
Volume 6, Issue 8, Pages 1218-1230Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/jamaoncol.2020.2134
Keywords
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Categories
Funding
- Cancer Research UK [C12292/A20861, C12292/A11174]
- Fondazione AIRC (Associazione Italiana Ricerca sul Cancro) under IG 2018 [21389]
- Italian Ministry of Education, Universities and Research-Dipartimenti di Eccellenza [L. 232/2016]
- Breast Cancer Family Registry from the NCI [UM1 CA164920]
- Research Council of Lithuania [SEN-18/2015]
- Breast Cancer Research Foundation
- Spanish Ministry of Health - FEDER funds [PI16/00440]
- Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2014-57680-R]
- Spanish Research Network on Rare Diseases (CIBERER)
- NCI of the NIH [R25CA112486, RC4CA153828]
- Fondazione AIRC (Associazione Italiana Ricerca sul Cancro, IG2014) [15547]
- Italian Ministry of Health
- MH CZ-DRO (MMCI) [00209805, LM2018125]
- European Union (European Social Fund)
- Greek national funds through the Operational Program Education and Lifelong Learning of the National Strategic Reference Framework-Research Funding Program of the General Secretariat for Research and Technology [SYN11_10_19]
- German Cancer Research Center
- Cancer Research UK grants [C1287/A10118, C1287/A11990]
- Manchester NIHR Biomedical Research Centre [IS-BRC-1215-20007]
- University of Kansas Cancer Center [P30 CA168524]
- Kansas Bioscience Authority Eminent Scholar Program
- Chancellors Distinguished Chair in Biomedical Sciences Professorship
- Spanish Health Research Foundation
- Instituto de Salud Carlos III (ISCIII) - FEDER funds, through the Research Activity Intensification Program [INT15/00070, INT16/00154, INT17/00133]
- Instituto de Salud Carlos III (ISCIII) - FEDER funds, through Centro de Investigacion Biomedica en Red de Enferemdades Raras CIBERER [ACCI 2016: ER17P1AC7112/2018]
- Autonomous Government of Galicia (Consolidation and Structuring Program) [IN607B]
- Fundacion Mutua Madrilena
- German Cancer Aid [110837]
- French National Institute of Cancer (INCa, PHRC Ile de France) [AOR 01 082, 2013-1-BCB-01-ICH-1]
- Association Le cancer du sein, parlons-en! Award (2004)
- Association for International Cancer Research (2008-2010)
- Fondation ARC pour la recherche sur le cancer [PJA 20151203365]
- Canadian Institute of Health Research for the CIHR Team in Familial Risks of Breast Cancer program (2008-2013)
- European Commission FP7, Project Collaborative Ovarian, breast and prostate Gene-environment Study (COGS), large-scale integrating project (2009-2013)
- INCa grant [SHS-E-SP 18-015]
- Georgetown: the Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI) [P30-CA051008]
- Fisher Center for Hereditary Cancer and Clinical Genomics Research
- Swing For the Cure
- Spanish Ministry of Health [PI15/00059, PI16/01292]
- CIBERONC from ISCIII (Spain) - European Regional Development FEDER funds [CB-161200301]
- Helsinki University Hospital Research Fund
- Finnish Cancer Society
- Sigrid Juselius Foundation
- Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]
- Netherlands Organisation of Scientific Research grant [NWO 91109024]
- Pink Ribbon grants [110005, 2014-187.WO76]
- BBMRI grant [NWO 184.021.007/CP46]
- Transcan grant JTC 2012 Cancer [12-054]
- Dr Ellen Li Charitable Foundation
- Kerry Kuok Foundation
- Hong Kong Hereditary Breast Cancer Family Registry
- Hungarian Breast and Ovarian Cancer Study: Hungarian Research Grants [KTIA-OTKA CK-80745, OTKA K-112228, TUDFO/51757/2019-ITM]
- Asociacion Espanola Contra el Cancer (AECC)
- Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economia y Competitividad)
- Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa [PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563, PI18/01029]
- Institut Catala de la Salut and Autonomous Government of Catalonia [2009SGR290, 2014SGR338, 2017SGR449]
- Icelandic Association Walking for Breast Cancer Research
- Landspitali University Hospital Research Fund
- Ministero della Salute
- 5x1000 Istituto Oncologico Veneto grant
- Liga Portuguesa Contra o Cancro
- National Breast Cancer Foundation
- National Health and Medical Research Council
- Queensland Cancer Fund
- Cancer Council of New SouthWales
- Cancer Council of Victoria
- Cancer Council of Tasmania
- Cancer Council of South Australia
- Cancer Foundation ofWestern Australia
- NIH [CA116167, CA192393, CA176785]
- NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201, CA125183, R01 CA142996, 1U01CA161032]
- Robert and Kate Niehaus Clinical Cancer Genetics Initiative
- Andrew Sabin Research Fund
- Cancer Center Support Grant/Core Grant [P30 CA008748]
- Intramural Research Program of the US National Cancer Institute, NIH
- Westat, Inc, Rockville, MD [NO2-CP-11019-50, N02-CP-21013-63, N02-CP-65504]
- Ohio State University Comprehensive Cancer Center
- Italian Association of Cancer Research (AIRC) (IG 2013) [14477]
- Tuscany Institute for Tumors grant 2014-2015-2016
- Fondazione Pisana per la Scienza
- Ministry of Science, Technology and Innovation
- Ministry of Higher Education [UM.C/HlR/MOHE/06]
- Cancer Research Initiatives Foundation
- Swedish Cancer Society
- Ralph and Marion Falk Medical Research Trust
- Entertainment Industry Fund NationalWomen's Cancer Research Alliance
- Susan G. Komen Foundation for the Cure
- Basser Center for BRCA
- Hackers for Hope Pittsburgh
- Victorian Cancer Agency
- Cancer Australia
- [R0 1CA140323]
- [R01 CA214545]
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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. This cohort study compares the cancer spectrum and frequencies between male BRCA1 and BRCA2 pathogenic variant carriers. Question Are there cancer phenotype differences between male BRCA1 and BRCA2 pathogenic variant carriers? Findings In this cohort study of 6902 men with a BRCA1 or BRCA2 pathogenic variant, being affected by cancer, particularly breast, prostate, and pancreatic cancers and developing multiple primary tumors, was associated with a higher probability for a man of being a BRCA2, rather than a BRCA1, pathogenic variant carrier. Meaning Surveillance programs in men with BRCA1 and BRCA2 pathogenic variants should be tailored in light of these gene-specific cancer phenotype differences. These results may inform the design of prospective studies on cancer risks in male BRCA1 and BRCA2 pathogenic variant carriers.
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