Page 27 - EJMO-9-1

Eurasian Journal of Medicine and
Oncology
BRCA VUS in breast cancer in MENA region

3. Results Interestingly, we observed notable regional variations in
the distribution of VUS between BRCA1 and BRCA2 genes.
We identified 480 studies through electronic database The prevalence of BRCA1 VUS was higher in North African
searches and manual searching of reference lists and populations, where it was found in 13.48% (158/1,172) of
related systematic reviews. After removing duplicates, we cases, compared to 2.68% (129/4,812) in the Middle Eastern
screened 128 articles based on their titles and abstracts. populations. Conversely, BRCA2 VUS exhibited a markedly
Following this, 91 full-text articles were retrieved and different pattern, with a slightly higher prevalence in North
assessed against the predefined inclusion criteria, leaving African populations (8.02%, 94/1,172) compared to Middle
34 articles eligible for inclusion in this systematic review. Eastern populations (6.23%, 300/4,812).
The PRISMA diagram detailing the identification and
selection process is depicted in Figure 1. Analysis of BRCA1 VUS revealed distinct regional
patterns across the MENA region. In North African
3.1. Overview of the eligible studies populations, three VUS were particularly prevalent:

The database search yielded 34 relevant references that c.2082C>T, observed in 12.65% (20/158) of cases, 15,25,26,28
closely aligned with the inclusion criteria and were c.5117G>C, found in 6.96% (11/158) of cases, 19-21,23-25,29
15,26
included in this review. Geographically, studies from and c.5152+66G>A detected in 5% (8/158) of the cases.
Middle Eastern countries (n = 18) slightly outnumbered In contrast, the Middle Eastern populations exhibited
those from North African countries (n = 16). The included a different spectrum of frequent BRCA1 VUS, including
31
40,42
studies were conducted in Morocco (n = 5), 15-19 Algeria c.31G>T (3.87%, 5/129), c.4132G>A (3.1%, 4/129),
38,41,42
(n = 3), 20-22 and Tunisia (n = 8) 23-30 in North Africa. In the c.536A>G (3.1%, 4/129), c.1648A>C (3.1%,
38,42,50
42
Middle East, studies were conducted in Egypt (n = 1), 4/129), and c.1456T>C (3.1%, 4/129).
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Jordan (n = 2), 32,33 Saudi Arabia (n = 3), 34-36 Bahrain (n = 1), In North Africa, two BRCA2 VUS were most recurrent:
37
Iraq (n = 1), Lebanon (n = 4), 39-42 Cyprus (n = 2), 43,44 and c.67+62T>G, observed in 3.19% (3/94) of cases, 15,26
38
Turkey (n = 4). 45-48 Details of these studies are presented in c.865A>C, also detected in 3.19% (3/94) of cases. 15,23,28
Table 1. Notably, the majority of BRCA2 VUS in this region
exhibited low frequencies, with 64.89% (61/94) of variants
Overall, 27 studies investigated both BRCA1 and being observed only once, while 13.83% (13/94) were
BRCA2, 15-18,20,22,23,26,28-30,32,33,35,37-49 four studies examined the detected twice. In contrast, the Middle Eastern populations
entire coding regions of BRCA1, 19,21,24,25 and three studies demonstrated a different spectrum of frequent BRCA2 VUS,
analyzed only a few BRCA1 and/or BRCA2 exons. 27,31,50 including IVS12_120T>C (12.33%, 37/300), c.9976A>T
39
Regarding methodological approaches, 61.76% (n = 21) of (5.33%, 16/300), 37,46 IVS11+80delTTAA (3.33%, 10/300),
39
the studies employed direct sequencing techniques, while c.739A>T (3% 9/300), and c.6322C>T (2.67%, 8/300). 39,40,44
31
38.24% (n = 13) utilized next-generation sequencing (NGS)
technologies. Notably, a significant shift in methodological The overall prevalence of BRCA1 and BRCA2 VUS
preference was observed in the pooled studies, with NGS across the MENA region is approximately 11.38%. This
techniques becoming increasingly prevalent from 2017 figure represents a significant proportion of the genetic
onwards. This trend reflects the broader adoption of high- variations found in BC patients within these areas. The
throughput sequencing technologies in genetic research, distribution of VUS across the MENA region shows
enabling more comprehensive and efficient analysis of considerable variation among different countries, with
complex genomic regions. some nations reporting a higher number of distinct VUS,
while others identifying fewer variants.
3.2. Distribution and prevalence of VUS in BRCA1 While it is challenging to determine a single
and BRCA2 in the MENA region
representative frequency for the entire Middle East, our
We conducted a comprehensive analysis of BRCA1 and data indicates that VUS comprises approximately 8.91% of
BRCA2 variants across various geographical regions in the the BRCA1 and BRCA2 variants detected in this subregion.
MENA region. Our analysis encompassed a total of 5984 In contrast, North Africa exhibits a markedly higher
individuals, with 1172 participants from North African prevalence, with VUS accounting for approximately 21.5%
studies and 4812 individuals from Middle Eastern studies. of the BRCA1 and BRCA2 variants.
Among these individuals, we identified 681 carriers of
VUS, representing 385 distinct VUS within this population. 3.3. Distributions of VUS in BRCA1 and BRCA2
A visual summary of these findings is provided in Figure 2, The distribution of the 151 distinct BRCA1 variants reveals
while detailed information on BRCA1 and BRCA2 VUS is significant clustering in specific regions of the gene. Exons
presented in Table 2. 10 and 11 are the most frequently affected, representing

Volume 9 Issue 1 (2025) 19 doi: 10.36922/ejmo.5800