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)

Valentina Silvestri; Goska Leslie; Daniel R Barnes; CIMBA Group; Liene Ņikitina-Zaķe

doi:10.1001/jamaoncol.2020.2134

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)

Valentina Silvestri, Goska Leslie, Daniel R Barnes, CIMBA Group, Liene Ņikitina-Zaķe (Member of the Working Group)

Research output: Contribution to journal › Article › peer-review

44 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1218-1230
Number of pages	13
Journal	JAMA Oncology
Volume	6
Issue number	8
DOIs	https://doi.org/10.1001/jamaoncol.2020.2134
Publication status	Published - 1 Aug 2020
Externally published	Yes

Field of Science*

3.2 Clinical medicine

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1001/jamaoncol.2020.2134

Cite this

@article{8002d37c367d44099132986fb9af50a0,

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)",

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.",

author = "Valentina Silvestri and Goska Leslie and Barnes, {Daniel R} and {CIMBA Group} and Agnarsson, {Bjarni A} and Kristiina Aittom{\"a}ki and Elisa Alducci and Andrulis, {Irene L} and Barkardottir, {Rosa B} and Alicia Barroso and Daniel Barrowdale and Javier Benitez and Bernardo Bonanni and Ake Borg and Buys, {Saundra S} and Trinidad Cald{\'e}s and Caligo, {Maria A} and Carlo Capalbo and Ian Campbell and Chung, {Wendy K} and Claes, {Kathleen B M} and Colonna, {Sarah V} and Laura Cortesi and Couch, {Fergus J} and {de la Hoya}, Miguel and Orland Diez and Ding, {Yuan Chun} and Susan Domchek and Easton, {Douglas F} and Bent Ejlertsen and Christoph Engel and Evans, {D Gareth} and Lidia Feliubadal{\`o} and Lenka Foretova and Florentia Fostira and Lajos G{\'e}czi and Anne-Marie Gerdes and Gord Glendon and Godwin, {Andrew K.} and Goldgar, {David E.} and Eric Hahnen and Hogervorst, {Frans B. L.} and Hopper, {John L.} and Hulick, {Peter J.} and Claudine Isaacs and Angel Izquierdo and James, {Paul A} and Ramunas Janavicius and Jensen, {Uffe Birk} and John, {Esther M} and Vijai Joseph and Liene Ņikitina-Zaķe",

note = "Funding Information: The CIMBA data management and data analysis were supported by Cancer Research UK grants (C12292/A20861, C12292/ A11174). The research leading to these results has received funding from Fondazione AIRC (Associazione Italiana Ricerca sul Cancro) under IG 2018-ID. 21389 project-P.I. Ottini Laura and Italian Ministry of Education, Universities and Research- Dipartimenti di Eccellenza-L. 232/2016. Publisher Copyright: {\textcopyright} 2020 American Medical Association. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = aug,

day = "1",

doi = "10.1001/jamaoncol.2020.2134",

language = "English",

volume = "6",

pages = "1218--1230",

journal = "JAMA Oncology",

issn = "2374-2437",

publisher = "American Medical Association",

number = "8",

}

TY - JOUR

T1 - Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants

T2 - Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

AU - Silvestri, Valentina

AU - Leslie, Goska

AU - Barnes, Daniel R

AU - CIMBA Group

A2 - Agnarsson, Bjarni A

A2 - Aittomäki, Kristiina

A2 - Alducci, Elisa

A2 - Andrulis, Irene L

A2 - Barkardottir, Rosa B

A2 - Barroso, Alicia

A2 - Barrowdale, Daniel

A2 - Benitez, Javier

A2 - Bonanni, Bernardo

A2 - Borg, Ake

A2 - Buys, Saundra S

A2 - Caldés, Trinidad

A2 - Caligo, Maria A

A2 - Capalbo, Carlo

A2 - Campbell, Ian

A2 - Chung, Wendy K

A2 - Claes, Kathleen B M

A2 - Colonna, Sarah V

A2 - Cortesi, Laura

A2 - Couch, Fergus J

A2 - de la Hoya, Miguel

A2 - Diez, Orland

A2 - Ding, Yuan Chun

A2 - Domchek, Susan

A2 - Easton, Douglas F

A2 - Ejlertsen, Bent

A2 - Engel, Christoph

A2 - Evans, D Gareth

A2 - Feliubadalò, Lidia

A2 - Foretova, Lenka

A2 - Fostira, Florentia

A2 - Géczi, Lajos

A2 - Gerdes, Anne-Marie

A2 - Glendon, Gord

A2 - Godwin, Andrew K.

A2 - Goldgar, David E.

A2 - Hahnen, Eric

A2 - Hogervorst, Frans B. L.

A2 - Hopper, John L.

A2 - Hulick, Peter J.

A2 - Isaacs, Claudine

A2 - Izquierdo, Angel

A2 - James, Paul A

A2 - Janavicius, Ramunas

A2 - Jensen, Uffe Birk

A2 - John, Esther M

A2 - Joseph, Vijai

A2 - Ņikitina-Zaķe, Liene

N1 - Funding Information: The CIMBA data management and data analysis were supported by Cancer Research UK grants (C12292/A20861, C12292/ A11174). The research leading to these results has received funding from Fondazione AIRC (Associazione Italiana Ricerca sul Cancro) under IG 2018-ID. 21389 project-P.I. Ottini Laura and Italian Ministry of Education, Universities and Research- Dipartimenti di Eccellenza-L. 232/2016. Publisher Copyright: © 2020 American Medical Association. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/8/1

Y1 - 2020/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85088708548&partnerID=8YFLogxK

U2 - 10.1001/jamaoncol.2020.2134

DO - 10.1001/jamaoncol.2020.2134

M3 - Article

C2 - 32614418

SN - 2374-2437

VL - 6

SP - 1218

EP - 1230

JO - JAMA Oncology

JF - JAMA Oncology

IS - 8

ER -

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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