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; Bjarni A. Agnarsson; Kristiina Aittomäki; Elisa Alducci; Irene L. Andrulis; Rosa B. Barkardottir; Alicia Barroso; Daniel Barrowdale; Javier Benitez; Bernardo Bonanni; Ake Borg; Saundra S. Buys; Trinidad Caldés; Maria A. Caligo; Carlo Capalbo; Ian Campbell; Wendy K. Chung; Kathleen B.M. Claes; Sarah V. Colonna; Laura Cortesi; Fergus J. Couch; Miguel De La Hoya; Orland Diez; Yuan Chun Ding; Susan Domchek; Douglas F. Easton; Bent Ejlertsen; Christoph Engel; D. Gareth Evans; Lidia Feliubadalò; Lenka Foretova; Florentia Fostira; Lajos Géczi; Anne Marie Gerdes; Gord Glendon; Andrew K. Godwin; David E. Goldgar; Eric Hahnen; Frans B.L. Hogervorst; John L. Hopper; Peter J. Hulick; Claudine Isaacs; Angel Izquierdo; Paul A. James; Ramunas Janavicius; Uffe Birk Jensen; Esther M. John; Vijai Joseph; Irene Konstantopoulou; Allison W. Kurian; Ava Kwong; Elisabetta Landucci; Fabienne Lesueur; Jennifer T. Loud; Eva Machackova; Phuong L. Mai; Keivan Majidzadeh-A; Siranoush Manoukian; Marco Montagna; Lidia Moserle; Anna Marie Mulligan; Katherine L. Nathanson; Heli Nevanlinna; Joanne Ngeow Yuen Ye; Liene Nikitina-Zake; Kenneth Offit; Edith Olah; Olufunmilayo I. Olopade; Ana Osorio; Laura Papi; Sue K. Park; Inge Sokilde Pedersen; Pedro Perez-Segura; Annabeth H. Petersen; Pedro Pinto; Berardino Porfirio; Miquel Angel Pujana; Paolo Radice; Johanna Rantala; Muhammad U. Rashid; Barak Rosenzweig; Maria Rossing; Marta Santamariña; Rita K. Schmutzler; Leigha Senter; Jacques Simard; Christian F. Singer; Angela R. Solano; Melissa C. Southey; Linda Steele; Zoe Steinsnyder; Dominique Stoppa-Lyonnet; Yen Yen Tan; Manuel R. Teixeira; Soo H. Teo; Mary Beth Terry; Mads Thomassen; Amanda E. Toland; Sara Torres-Esquius; Nadine Tung; Christi J. Van Asperen; Ana Vega; Alessandra Viel; Jeroen Vierstraete; Barbara Wappenschmidt; Jeffrey N. Weitzel; Greet Wieme; Sook Yee Yoon; Kristin K. Zorn; Lesley Mcguffog; Michael T. Parsons; Ute Hamann; Mark H. Greene; Judy A. Kirk; Susan L. Neuhausen; Timothy R. Rebbeck; Marc Tischkowitz; Georgia Chenevix-Trench; Antonis C. Antoniou; Eitan Friedman; Laura Ottini

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, Bjarni A. Agnarsson, Kristiina Aittomäki, Elisa Alducci, Irene L. Andrulis, Rosa B. Barkardottir, Alicia Barroso, Daniel Barrowdale, Javier Benitez, Bernardo Bonanni, Ake Borg, Saundra S. Buys, Trinidad Caldés, Maria A. Caligo, Carlo Capalbo, Ian Campbell, Wendy K. Chung, Kathleen B.M. ClaesSarah V. Colonna, Laura Cortesi, Fergus J. Couch, Miguel De La Hoya, Orland Diez, Yuan Chun Ding, Susan Domchek, Douglas F. Easton, Bent Ejlertsen, Christoph Engel, D. Gareth Evans, Lidia Feliubadalò, Lenka Foretova, Florentia Fostira, Lajos Géczi, Anne Marie Gerdes, Gord Glendon, Andrew K. Godwin, David E. Goldgar, Eric Hahnen, Frans B.L. Hogervorst, John L. Hopper, Peter J. Hulick, Claudine Isaacs, Angel Izquierdo, Paul A. James, Ramunas Janavicius, Uffe Birk Jensen, Esther M. John, Vijai Joseph, Irene Konstantopoulou, Allison W. Kurian, Ava Kwong, Elisabetta Landucci, Fabienne Lesueur, Jennifer T. Loud, Eva Machackova, Phuong L. Mai, Keivan Majidzadeh-A, Siranoush Manoukian, Marco Montagna, Lidia Moserle, Anna Marie Mulligan, Katherine L. Nathanson, Heli Nevanlinna, Joanne Ngeow Yuen Ye, Liene Nikitina-Zake, Kenneth Offit, Edith Olah, Olufunmilayo I. Olopade, Ana Osorio, Laura Papi, Sue K. Park, Inge Sokilde Pedersen, Pedro Perez-Segura, Annabeth H. Petersen, Pedro Pinto, Berardino Porfirio, Miquel Angel Pujana, Paolo Radice, Johanna Rantala, Muhammad U. Rashid, Barak Rosenzweig, Maria Rossing, Marta Santamariña, Rita K. Schmutzler, Leigha Senter, Jacques Simard, Christian F. Singer, Angela R. Solano, Melissa C. Southey, Linda Steele, Zoe Steinsnyder, Dominique Stoppa-Lyonnet, Yen Yen Tan, Manuel R. Teixeira, Soo H. Teo, Mary Beth Terry, Mads Thomassen, Amanda E. Toland, Sara Torres-Esquius, Nadine Tung, Christi J. Van Asperen, Ana Vega, Alessandra Viel, Jeroen Vierstraete, Barbara Wappenschmidt, Jeffrey N. Weitzel, Greet Wieme, Sook Yee Yoon, Kristin K. Zorn, Lesley Mcguffog, Michael T. Parsons, Ute Hamann, Mark H. Greene, Judy A. Kirk, Susan L. Neuhausen, Timothy R. Rebbeck, Marc Tischkowitz, Georgia Chenevix-Trench, Antonis C. Antoniou, Eitan Friedman, Laura Ottini

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

6 Scopus citations

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 (US)
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
State	Published - Aug 2020

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1001/jamaoncol.2020.2134

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Silvestri, V., Leslie, G., Barnes, D. R., Agnarsson, B. A., Aittomäki, K., Alducci, E., Andrulis, I. L., Barkardottir, R. B., Barroso, A., Barrowdale, D., Benitez, J., Bonanni, B., Borg, A., Buys, S. S., Caldés, T., Caligo, M. A., Capalbo, C., Campbell, I., Chung, W. K., ... Ottini, L. (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, 6(8), 1218-1230. https://doi.org/10.1001/jamaoncol.2020.2134

Silvestri, V, Leslie, G, Barnes, DR, Agnarsson, BA, Aittomäki, K, Alducci, E, Andrulis, IL, Barkardottir, RB, Barroso, A, Barrowdale, D, Benitez, J, Bonanni, B, Borg, A, Buys, SS, Caldés, T, Caligo, MA, Capalbo, C, Campbell, I, Chung, WK, Claes, KBM, Colonna, SV, Cortesi, L, Couch, FJ, De La Hoya, M, Diez, O, Ding, YC, Domchek, S, Easton, DF, Ejlertsen, B, Engel, C, Evans, DG, Feliubadalò, L, Foretova, L, Fostira, F, Géczi, L, Gerdes, AM, Glendon, G, Godwin, AK, Goldgar, DE, Hahnen, E, Hogervorst, FBL, Hopper, JL, Hulick, PJ, Isaacs, C, Izquierdo, A, James, PA, Janavicius, R, Jensen, UB, John, EM, Joseph, V, Konstantopoulou, I, Kurian, AW, Kwong, A, Landucci, E, Lesueur, F, Loud, JT, Machackova, E, Mai, PL, Majidzadeh-A, K, Manoukian, S, Montagna, M, Moserle, L, Mulligan, AM, Nathanson, KL, Nevanlinna, H, Ngeow Yuen Ye, J, Nikitina-Zake, L, Offit, K, Olah, E, Olopade, OI, Osorio, A, Papi, L, Park, SK, Pedersen, IS, Perez-Segura, P, Petersen, AH, Pinto, P, Porfirio, B, Pujana, MA, Radice, P, Rantala, J, Rashid, MU, Rosenzweig, B, Rossing, M, Santamariña, M, Schmutzler, RK, Senter, L, Simard, J, Singer, CF, Solano, AR, Southey, MC, Steele, L, Steinsnyder, Z, Stoppa-Lyonnet, D, Tan, YY, Teixeira, MR, Teo, SH, Terry, MB, Thomassen, M, Toland, AE, Torres-Esquius, S, Tung, N, Van Asperen, CJ, Vega, A, Viel, A, Vierstraete, J, Wappenschmidt, B, Weitzel, JN, Wieme, G, Yoon, SY, Zorn, KK, Mcguffog, L, Parsons, MT, Hamann, U, Greene, MH, Kirk, JA, Neuhausen, SL, Rebbeck, TR, Tischkowitz, M, Chenevix-Trench, G, Antoniou, AC, Friedman, E & Ottini, L 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

@article{eb0b8e26f0ab4fe188d995610e80e0e8,

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 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 Gerdes, {Anne Marie} 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 Irene Konstantopoulou and Kurian, {Allison W.} and Ava Kwong and Elisabetta Landucci and Fabienne Lesueur and Loud, {Jennifer T.} and Eva Machackova and Mai, {Phuong L.} and Keivan Majidzadeh-A and Siranoush Manoukian and Marco Montagna and Lidia Moserle and Mulligan, {Anna Marie} and Nathanson, {Katherine L.} and Heli Nevanlinna and {Ngeow Yuen Ye}, Joanne and Liene Nikitina-Zake and Kenneth Offit and Edith Olah and Olopade, {Olufunmilayo I.} and Ana Osorio and Laura Papi and Park, {Sue K.} and Pedersen, {Inge Sokilde} and Pedro Perez-Segura and Petersen, {Annabeth H.} and Pedro Pinto and Berardino Porfirio and Pujana, {Miquel Angel} and Paolo Radice and Johanna Rantala and Rashid, {Muhammad U.} and Barak Rosenzweig and Maria Rossing and Marta Santamari{\~n}a and Schmutzler, {Rita K.} and Leigha Senter and Jacques Simard and Singer, {Christian F.} and Solano, {Angela R.} and Southey, {Melissa C.} and Linda Steele and Zoe Steinsnyder and Dominique Stoppa-Lyonnet and Tan, {Yen Yen} and Teixeira, {Manuel R.} and Teo, {Soo H.} and Terry, {Mary Beth} and Mads Thomassen and Toland, {Amanda E.} and Sara Torres-Esquius and Nadine Tung and {Van Asperen}, {Christi J.} and Ana Vega and Alessandra Viel and Jeroen Vierstraete and Barbara Wappenschmidt and Weitzel, {Jeffrey N.} and Greet Wieme and Yoon, {Sook Yee} and Zorn, {Kristin K.} and Lesley Mcguffog and Parsons, {Michael T.} and Ute Hamann and Greene, {Mark H.} and Kirk, {Judy A.} and Neuhausen, {Susan L.} and Rebbeck, {Timothy R.} and Marc Tischkowitz and Georgia Chenevix-Trench and Antoniou, {Antonis C.} and Eitan Friedman and Laura Ottini",

year = "2020",

month = aug,

doi = "10.1001/jamaoncol.2020.2134",

language = "English (US)",

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 - Agnarsson, Bjarni A.

AU - Aittomäki, Kristiina

AU - Alducci, Elisa

AU - Andrulis, Irene L.

AU - Barkardottir, Rosa B.

AU - Barroso, Alicia

AU - Barrowdale, Daniel

AU - Benitez, Javier

AU - Bonanni, Bernardo

AU - Borg, Ake

AU - Buys, Saundra S.

AU - Caldés, Trinidad

AU - Caligo, Maria A.

AU - Capalbo, Carlo

AU - Campbell, Ian

AU - Chung, Wendy K.

AU - Claes, Kathleen B.M.

AU - Colonna, Sarah V.

AU - Cortesi, Laura

AU - Couch, Fergus J.

AU - De La Hoya, Miguel

AU - Diez, Orland

AU - Ding, Yuan Chun

AU - Domchek, Susan

AU - Easton, Douglas F.

AU - Ejlertsen, Bent

AU - Engel, Christoph

AU - Evans, D. Gareth

AU - Feliubadalò, Lidia

AU - Foretova, Lenka

AU - Fostira, Florentia

AU - Géczi, Lajos

AU - Gerdes, Anne Marie

AU - Glendon, Gord

AU - Godwin, Andrew K.

AU - Goldgar, David E.

AU - Hahnen, Eric

AU - Hogervorst, Frans B.L.

AU - Hopper, John L.

AU - Hulick, Peter J.

AU - Isaacs, Claudine

AU - Izquierdo, Angel

AU - James, Paul A.

AU - Janavicius, Ramunas

AU - Jensen, Uffe Birk

AU - John, Esther M.

AU - Joseph, Vijai

AU - Konstantopoulou, Irene

AU - Kurian, Allison W.

AU - Kwong, Ava

AU - Landucci, Elisabetta

AU - Lesueur, Fabienne

AU - Loud, Jennifer T.

AU - Machackova, Eva

AU - Mai, Phuong L.

AU - Majidzadeh-A, Keivan

AU - Manoukian, Siranoush

AU - Montagna, Marco

AU - Moserle, Lidia

AU - Mulligan, Anna Marie

AU - Nathanson, Katherine L.

AU - Nevanlinna, Heli

AU - Ngeow Yuen Ye, Joanne

AU - Nikitina-Zake, Liene

AU - Offit, Kenneth

AU - Olah, Edith

AU - Olopade, Olufunmilayo I.

AU - Osorio, Ana

AU - Papi, Laura

AU - Park, Sue K.

AU - Pedersen, Inge Sokilde

AU - Perez-Segura, Pedro

AU - Petersen, Annabeth H.

AU - Pinto, Pedro

AU - Porfirio, Berardino

AU - Pujana, Miquel Angel

AU - Radice, Paolo

AU - Rantala, Johanna

AU - Rashid, Muhammad U.

AU - Rosenzweig, Barak

AU - Rossing, Maria

AU - Santamariña, Marta

AU - Schmutzler, Rita K.

AU - Senter, Leigha

AU - Simard, Jacques

AU - Singer, Christian F.

AU - Solano, Angela R.

AU - Southey, Melissa C.

AU - Steele, Linda

AU - Steinsnyder, Zoe

AU - Stoppa-Lyonnet, Dominique

AU - Tan, Yen Yen

AU - Teixeira, Manuel R.

AU - Teo, Soo H.

AU - Terry, Mary Beth

AU - Thomassen, Mads

AU - Toland, Amanda E.

AU - Torres-Esquius, Sara

AU - Tung, Nadine

AU - Van Asperen, Christi J.

AU - Vega, Ana

AU - Viel, Alessandra

AU - Vierstraete, Jeroen

AU - Wappenschmidt, Barbara

AU - Weitzel, Jeffrey N.

AU - Wieme, Greet

AU - Yoon, Sook Yee

AU - Zorn, Kristin K.

AU - Mcguffog, Lesley

AU - Parsons, Michael T.

AU - Hamann, Ute

AU - Greene, Mark H.

AU - Kirk, Judy A.

AU - Neuhausen, Susan L.

AU - Rebbeck, Timothy R.

AU - Tischkowitz, Marc

AU - Chenevix-Trench, Georgia

AU - Antoniou, Antonis C.

AU - Friedman, Eitan

AU - Ottini, Laura

PY - 2020/8

Y1 - 2020/8

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

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

U2 - 10.1001/jamaoncol.2020.2134

DO - 10.1001/jamaoncol.2020.2134

M3 - Article

C2 - 32614418

AN - SCOPUS:85088708548

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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