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

2020

JAMA ONCOLOGY

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

01 Pubblicazione su rivista

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

DOI: 10.1001/jamaoncol.2020.2134

ISSN: 2374-2437

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.

BRCA cancer spectrum male cancers