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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | JAMA Oncology |
| Vol/bind | 6 |
| Udgave nummer | 8 |
| Sider (fra-til) | 1218-1230 |
| ISSN | 2374-2437 |
| DOI | |
| Status | Udgivet - 2020 |
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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). / Silvestri, Valentina; Leslie, Goska; Barnes, Daniel R.; Agnarsson, Bjarni A.; Aittomäki, Kristiina; Alducci, Elisa; Andrulis, Irene L.; Barkardottir, Rosa B.; Barroso, Alicia; Barrowdale, Daniel; Benitez, Javier; Bonanni, Bernardo; Borg, Ake; Buys, Saundra S.; Caldés, Trinidad; Caligo, Maria A.; Capalbo, Carlo; Campbell, Ian; Chung, Wendy K.; Claes, Kathleen B.M.; Colonna, Sarah V.; Cortesi, Laura; Couch, Fergus J.; De La Hoya, Miguel; Diez, Orland; Ding, Yuan Chun; Domchek, Susan; Easton, Douglas F.; Ejlertsen, Bent; Engel, Christoph; Evans, D. Gareth; Feliubadalò, Lidia; Foretova, Lenka; Fostira, Florentia; Géczi, Lajos; Gerdes, Anne Marie; Glendon, Gord; Godwin, Andrew K.; Goldgar, David E.; Hahnen, Eric; Hogervorst, Frans B.L.; Hopper, John L.; Hulick, Peter J.; Isaacs, Claudine; Izquierdo, Angel; James, Paul A.; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M.; Joseph, Vijai; Konstantopoulou, Irene; Kurian, Allison W.; Kwong, Ava; Landucci, Elisabetta; Lesueur, Fabienne; Loud, Jennifer T.; Machackova, Eva; Mai, Phuong L.; Majidzadeh-A, Keivan; Manoukian, Siranoush; Montagna, Marco; Moserle, Lidia; Mulligan, Anna Marie; Nathanson, Katherine L.; Nevanlinna, Heli; Ngeow Yuen Ye, Joanne; Nikitina-Zake, Liene; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Osorio, Ana; Papi, Laura; Park, Sue K.; Pedersen, Inge Sokilde; Perez-Segura, Pedro; Petersen, Annabeth H.; Pinto, Pedro; Porfirio, Berardino; Pujana, Miquel Angel; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad U.; Rosenzweig, Barak; Rossing, Maria; Santamariña, Marta; Schmutzler, Rita K.; Senter, Leigha; Simard, Jacques; Singer, Christian F.; Solano, Angela R.; Southey, Melissa C.; Steele, Linda; Steinsnyder, Zoe; Stoppa-Lyonnet, Dominique; Tan, Yen Yen; Teixeira, Manuel R.; Teo, Soo H.; Terry, Mary Beth; Thomassen, Mads; Toland, Amanda E.; Torres-Esquius, Sara; Tung, Nadine; Van Asperen, Christi J.; Vega, Ana; Viel, Alessandra; Vierstraete, Jeroen; Wappenschmidt, Barbara; Weitzel, Jeffrey N.; Wieme, Greet; Yoon, Sook Yee; Zorn, Kristin K.; Mcguffog, Lesley; Parsons, Michael T.; Hamann, Ute; Greene, Mark H.; Kirk, Judy A.; Neuhausen, Susan L.; Rebbeck, Timothy R.; Tischkowitz, Marc; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Friedman, Eitan; Ottini, Laura.
I: JAMA Oncology, Bind 6, Nr. 8, 2020, s. 1218-1230.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
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
Y1 - 2020
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.
U2 - 10.1001/jamaoncol.2020.2134
DO - 10.1001/jamaoncol.2020.2134
M3 - Journal article
C2 - 32614418
AN - SCOPUS:85088708548
VL - 6
SP - 1218
EP - 1230
JO - JAMA Oncology
JF - JAMA Oncology
SN - 2374-2437
IS - 8
ER -