Fol. Biol. 2024, 70, 274-284
Genetic Predisposition to Male Breast Cancer
, Marianna Borecká1,2, Petra Zemánková1,2,3, Kateřina Matějková2,4, Petr Nehasil1,2,3,5, Leona Černá1,6, Marta Černá1,2, Petra Dušková1,7, Taťána Doležalová2, Lenka Foretová1,8, Ondřej Havránek1,10,9, Jana Házová1,8, Klára Horáčková1,2, Milena Hovhannisyan1,2, Lucie Hrušková1,11, Štěpán Chvojka1,6, Mária Janíková1,12, Marta Kalousová2, Marcela Kosařová1,13, Monika Koudová1,6, Veronika Krhutová14, Veronika Krulišová1,11, Eva Macháčková1,8, Renáta Michalovská1,11, Barbora Němcová2, Jan Novotný1,10, Markéta Šafaříková2, Barbora Šťastná1,15,2, Viktor Stránecký1,5, Ivan Šubrt1,16, Spiros Tavandzis1,14, Zdeňka Vlčková1,11, Michal Vočka1,10,17, Radek Vrtěl1,12, Tomáš Zima2, Jana Soukupová1,2, Petra Kleiblová1,10,2, Zdeněk Kleibl1,2,3
1CZECANCA consortium, Czech Republic
2Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
3Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
4Department of Genetics and Microbiology, Faculty of Science, Charles University, Prague, Czech Republic
5Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
6Centre for Medical Genetics and Reproductive Medicine, GENNET, Prague, Czech Republic
7Laboratory of Molecular Biology and Genetics, Hospital Ceske Budejovice, Ceske Budejovice, Czech Republic
8Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
9BIOCEV, First Faculty of Medicine, Charles University, Prague, Czech Republic
10Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
11GHC Genetics, Prague, Czech Republic
12Department of Medical Genetics, Faculty of Medicine and Dentistry, University Hospital Olomouc, Palacky University Olomouc, Olomouc, Czech Republic
13Department of Medical Genetics, PRONATAL Sanatorium, Prague, Czech Republic
14Department of Medical Genetics, AGEL Laboratories, AGEL Research and Training Institute, Novy Jicin, Czech Republic
15Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic
16Department of Medical Genetics, Faculty of Medicine in Pilsen, Charles University and University Hospital Pilsen, Pilsen, Czech Republic
17Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague,
Received December 2024
Accepted January 2025
Male breast cancer (mBC) is a rare cancer diagnosis that constitutes less than 1 % of all breast cancer cases globally. Genetic factors play an important role in the mBC risk. Germline pathogenic variants (PVs) in cancer predisposition genes could be identified in about 15 % of cases. We performed germline genetic testing in 248 Czech mBC patients and 3,626 non-cancer male controls using next-generation sequencing by the CZECANCA panel (226 genes). We identified 46/248 (18.5 %) carriers of PVs in the established mBC predisposition genes, primarily in BRCA2 (N = 34), less frequently in BRCA1 (N = 7) and PALB2 (N = 5). The presence of a PV in these genes significantly increased the mBC risk (OR 44.04; 5.82; and 8.26, respectively). Additionally, we identified 16 carriers of PVs in candidate mBC genes, but only PVs in CHEK2 were significantly associated with increased mBC risk (OR = 4.98). The significance of 26 germline alterations in 23/192 additionally analysed genes remained uncertain. The carriers of PVs in BRCA1 and CHEK2 were significantly younger (55.8 and 52.6 years, respectively) than non-carriers (64.8 years), and all carriers of PVs in the established genes had more frequently grade G3 tumours and positive family cancer history. Our study underscores the critical role of BRCA2 in mBC predisposition while also highlighting the potential contributions of additional genes that warrant further investigation. Moreover, it supports and justifies universal genetic testing for all mBC patients to generally improve early cancer detection and tailored treatment.
Supplementary materials - Tables: S1, S2, S3, and S4
Funding
This study has been supported by the grant projects of the Ministry of Health of the Czech Republic: NU23-03-00150, NW24-03-00092, BBMRI_CZ LM2023033 and DRO-VFN-64165; Charles University projects: COOPERATIO, SVV260631, UNCE/24/MED/022; and the Ministry of Education Youth and Sports of the Czech Republic grant EXCELES No. LX22NPO5102.
References
Copyright
This is an open-access article distributed under the terms of the Creative Commons Attribution License.