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Article

Do BARD1 Mutations Confer an Elevated Risk of Prostate Cancer?

1
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland
2
Department of Clinical Genetics and Pathology, University of Zielona Góra, 65-417 Zielona Góra, Poland
3
Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland
4
Department of Histology, Department of Biology and Genetics, Faculty of Medicine, University of Opole, 45-040 Opole, Poland
5
Department of Pathology, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland
6
Department of Molecular Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Poland
7
Department of Gynecology and Obstetrics, Institute of Medical, Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
8
Collegium Medicum, University of Zielona Gora, 65-417 Zielona Gora, Poland
9
Women’s College Research Institute, Women’s College Hospital, University of Toronto, Toronto, ON M5G 1N8, Canada
10
Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5S 1A1, Canada
*
Authors to whom correspondence should be addressed.
Membership of the Polish Hereditary Prostate Cancer Consortium is provided in the Acknowledgments.
Academic Editor: Holger A. Sültmann
Cancers 2021, 13(21), 5464; https://doi.org/10.3390/cancers13215464
Received: 11 October 2021 / Revised: 26 October 2021 / Accepted: 28 October 2021 / Published: 30 October 2021
(This article belongs to the Special Issue Familial Cancer and Germline Genetics)
Current cancer testing gene panels tend to be comprehensive. One of the genes commonly included in the testing panels is BARD1. To establish whether BARD1 mutations predispose to prostate cancer, we sequenced BARD1 in 390 hereditary prostate cancer cases, genotyped 5715 men with unselected prostate cancer and 10,252 controls for three recurrent rare BARD1 variants in Poland. We did not see an elevated prostate risk cancer given p.Q564X truncating mutation, p.R658C missense mutation and p.R659= synonymous variant. Neither variant influenced prostate cancer characteristics or survival. Our study is the first to evaluate the association between BARD1 mutations and prostate cancer susceptibility. It is not justified to inform men about increased prostate cancer risk in case of identification of a BARD1 mutation. However, a female relative of a man with a BARD1 mutation may benefit from this information and be tested, because BARD1 is a breast cancer susceptibility gene.
The current cancer testing gene panels tend to be comprehensive rather than site-specific. BARD1 is one of the genes commonly included in the multi-cancer testing panels. Mutations in BARD1 confer an increase in the risk for breast cancer, but it is not studied whether or not they predispose to prostate cancer. To establish if BARD1 mutations also predispose to prostate cancer, we screened BARD1 in 390 Polish patients with hereditary prostate cancer. No truncating mutations were identified by sequencing. We also genotyped 5715 men with unselected prostate cancer, and 10,252 controls for three recurrent BARD1 variants, including p.Q564X, p.R658C and p.R659=. Neither variant conferred elevated risk of prostate cancer (ORs between 0.84 and 1.15, p-values between 0.57 and 0.93) nor did they influence prostate cancer characteristics or survival. We conclude that men with a BARD1 mutation are not at elevated prostate cancer risk. It is not justified to inform men about increased prostate cancer risk in case of identification of a BARD1 mutation. However, a female relative of a man with a BARD1 mutation may benefit from this information and be tested for the mutation, because BARD1 is a breast cancer susceptibility gene. View Full-Text
Keywords: BARD1; mutation; prostate cancer; risk; survival BARD1; mutation; prostate cancer; risk; survival
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MDPI and ACS Style

Stempa, K.; Wokołorczyk, D.; Kluźniak, W.; Rogoża-Janiszewska, E.; Malińska, K.; Rudnicka, H.; Huzarski, T.; Gronwald, J.; Gliniewicz, K.; Dębniak, T.; Jakubowska, A.; Lener, M.; Tomiczek-Szwiec, J.; Domagała, P.; Suszynska, M.; Kozlowski, P.; Kluz, T.; Naczk, M.; Lubiński, J.; Narod, S.A.; Akbari, M.R.; Cybulski, C.; on behalf of the Polish Hereditary Prostate Cancer Consortium. Do BARD1 Mutations Confer an Elevated Risk of Prostate Cancer? Cancers 2021, 13, 5464. https://doi.org/10.3390/cancers13215464

AMA Style

Stempa K, Wokołorczyk D, Kluźniak W, Rogoża-Janiszewska E, Malińska K, Rudnicka H, Huzarski T, Gronwald J, Gliniewicz K, Dębniak T, Jakubowska A, Lener M, Tomiczek-Szwiec J, Domagała P, Suszynska M, Kozlowski P, Kluz T, Naczk M, Lubiński J, Narod SA, Akbari MR, Cybulski C, on behalf of the Polish Hereditary Prostate Cancer Consortium. Do BARD1 Mutations Confer an Elevated Risk of Prostate Cancer? Cancers. 2021; 13(21):5464. https://doi.org/10.3390/cancers13215464

Chicago/Turabian Style

Stempa, Klaudia, Dominika Wokołorczyk, Wojciech Kluźniak, Emilia Rogoża-Janiszewska, Karolina Malińska, Helena Rudnicka, Tomasz Huzarski, Jacek Gronwald, Katarzyna Gliniewicz, Tadeusz Dębniak, Anna Jakubowska, Marcin Lener, Joanna Tomiczek-Szwiec, Paweł Domagała, Malwina Suszynska, Piotr Kozlowski, Tomasz Kluz, Mariusz Naczk, Jan Lubiński, Steven A. Narod, Mohammad R. Akbari, Cezary Cybulski, and on behalf of the Polish Hereditary Prostate Cancer Consortium. 2021. "Do BARD1 Mutations Confer an Elevated Risk of Prostate Cancer?" Cancers 13, no. 21: 5464. https://doi.org/10.3390/cancers13215464

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