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)

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dc.contributor.author CIMBA Grp
dc.contributor.author Silvestri, Valentina
dc.contributor.author Leslie, Goska
dc.contributor.author Barnes, Daniel R.
dc.contributor.author Aittomäki, Kristiina
dc.contributor.author Nevanlinna, Heli
dc.date.accessioned 2021-07-21T22:40:55Z
dc.date.available 2021-12-18T03:45:10Z
dc.date.issued 2020-08
dc.identifier.citation CIMBA Grp , Silvestri , V , Leslie , G , Barnes , D R , Aittomäki , K & Nevanlinna , H 2020 , ' 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) ' , JAMA Oncology , vol. 6 , no. 8 , pp. 1218-1230 . https://doi.org/10.1001/jamaoncol.2020.2134
dc.identifier.other PURE: 144693517
dc.identifier.other PURE UUID: 886197a3-6881-49ff-a9f9-651a8ec0d6c2
dc.identifier.other WOS: 000562846800010
dc.identifier.uri http://hdl.handle.net/10138/332518
dc.description.abstract 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. en
dc.format.extent 13
dc.language.iso eng
dc.relation.ispartof JAMA Oncology
dc.rights unspecified
dc.rights unspecified
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject GENE-ENVIRONMENT INTERACTION
dc.subject PROSTATE-CANCER
dc.subject BREAST-CANCER
dc.subject MUTATION CARRIERS
dc.subject RISK
dc.subject GUIDELINES
dc.subject 3122 Cancers
dc.title 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) en
dc.type Article
dc.contributor.organization Medicum
dc.contributor.organization Kristiina Aittomäki / Principal Investigator
dc.contributor.organization HUSLAB
dc.contributor.organization Department of Medical and Clinical Genetics
dc.contributor.organization Helsinki University Hospital Area
dc.contributor.organization University of Helsinki
dc.contributor.organization HUS Gynecology and Obstetrics
dc.contributor.organization Biosciences
dc.contributor.organization Department of Obstetrics and Gynecology
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1001/jamaoncol.2020.2134
dc.relation.issn 2374-2437
dc.rights.accesslevel openAccess
dc.type.version acceptedVersion
dc.type.version publishedVersion

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