Prevalence of Germline BRCA1/2 Variants in Ashkenazi and Non-Ashkenazi Prostate Cancer Populations: A Systematic Review and Meta-Analysis
by
, and
Antonio Cioffi
1, 
Ottavio De Cobelli
1,2,
Paolo Veronesi
2,3,
Carlo La Vecchia
4
,
Patrick Maisonneuve
5 and
Giovanni Corso
2,3,6,* 1
Division of Urology, European Institute of Oncology (IEO), IRCCS, 20141 Milan, Italy
2
Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy
3
Division of Breast Surgery, European Institute of Oncology (IEO), IRCCS, 20141 Milan, Italy
4
Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
5
Division of Epidemiology and Biostatistics, European Institute of Oncology (IEO), IRCCS, 20141 Milan, Italy
6
European Cancer Prevention Organization (ECP), 20122 Milan, Italy
*
Author to whom correspondence should be addressed.
Cancers 2023, 15(1), 306; https://doi.org/10.3390/cancers15010306
Submission received: 23 November 2022
/
Revised: 27 December 2022
/
Accepted: 29 December 2022
/
Published: 2 January 2023
(This article belongs to the Special Issue Genes in Cancer)
Simple Summary
Germline BRCA2 pathogenic variant carriers are associated with prostate cancer risk. Ashkenazi Jewish people are at higher risk of breast cancer due to the high prevalence of specific founder germline BRCA1/2 variants. The distribution of these variants (BRCA1 vs. BRCA2) in Ashkenazi men with prostate cancer is not clear. This systematic review and meta-analysis indicates that germline BRCA1 variants are higher in the Ashkenazi Jewish ethnicity in comparison to non-Ashkenazi men. Instead, BRCA2 variants present a similar distribution between the two considered groups.
Abstract
Background and aims: International guidelines recommend testing BRCA2 in men with prostate cancer, due to the presence of a strong association with this gene. Some ethnicities present disparities in genetic distribution for the relation with specific founder variants. Ashkenazi Jewish people are, importantly, at high risk of breast cancer for their inherited cluster with germline BRCA1/2 variants. However, in Ashkenazi men with prostate cancer, the prevalence of BRCA1 and/or BRCA2 is not well defined. We assessed the frequency of these variants in Ashkenazi vs. non-Ashkenazi men with prostate cancer. Materials and Methods: In accord with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, we revised all germline BRCA variants reported in MEDLINE from 1996 to 2021 in Ashkenazi and non-Ashkenazi men with prostate cancer. Results: Thirty-five original studies were selected for the analysis. Among populations from Israel and North America, Ashkenazi Jewish men presented higher prevalence of BRCA1 variants [0.9% (0.4–1.5) vs. 0.5% (0.2–1.1), p = 0.09] and a lower prevalence of BRCA2 variants [1.5% (1.1–2.0) vs. 3.5% (1.7–5.9), p = 0.08] in comparison to the non-Ashkenazi population. Conclusions: Since germline BRCA1 variants are more prevalent and BRCA2 variants are less prevalent in PCa patients of Ashkenazi Jewish ethnicity in comparison to non-Ashkenazi patients, prostate cancer genetic screening in Ashkenazi men should not be restricted to the BRCA2 gene.
Keywords:
prostate cancer; BRCA1 mutations; BRCA2 mutations; Ashkenazi; meta-analysis
