Page 25 - EJMO-9-1

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

1. Introduction process. To address the complexity of VUS, the American
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College of Medical Genetics and Genomics and the
Breast cancer (BC) is a global health challenge with Association for Molecular Pathology released guidelines
significant morbidity and mortality, affecting millions in 2015 for reclassifying VUS in BRCA1 and BRCA2.
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of individuals each year. The disease occurs worldwide, These guidelines provide a framework for determining
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impacting women of all ages after puberty. As of the end the clinical significance of VUS, classifying them into one
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of 2022, approximately 8.17 million women who had been of five categories: pathogenic, likely pathogenic, VUS,
diagnosed with BC in the past 5 years remained alive, likely benign, or benign. The reclassification of VUS can
making it the most prevalent cancer globally. According help reduce uncertainty in clinical interpretation and
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to the GLOBOCAN Cancer Tomorrow prediction tool, minimize the proportion of VUS in clinical testing data.
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incident cases are expected to increase by more than Reclassification can be based on various factors, including
46.5% by 2045. This growing global burden of BC is
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mainly observed in low- and middle-income countries, clinical data, functional assays, computational predictions,
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particularly among women under the age of 50. 3 and population frequency.
In the Middle East and North Africa (MENA) region, The prevalence of BRCA1 and BRCA2 VUS in BC
BC incidence rates have been rising rapidly, with a notably patients in the MENA region is not well-documented.
younger median age of onset compared to Western Nevertheless, the occurrence of VUS is not uncommon.
countries. Genetic factors, particularly mutations in the The purpose of this review is twofold: first, to establish the
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BC genes (BRCA) 1 and 2, play a significant role in BC current knowledge regarding BRCA VUS and to determine
susceptibility, especially in cases of early-onset and familial the spectrum of these variants in BRCA1 and BRCA2 in
BC. 5 BC; and second, to reclassify and evaluate the current
understanding of BRCA1 and BRCA2 VUS in BC patients
BRCA1 and BRCA2 are the most commonly recognized in the MENA region.
genes associated with hereditary BC and/or ovarian
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cancer (OC) risk. Individuals with inherited pathogenic 2. Methods
variants in BRCA1 or BRCA2 are at significantly higher 2.1. Study design
lifetime risk for developing BC and OC and may face
treatment options ranging from prophylactic surgery to This study is a systematic review of the prevalence of
increased surveillance. However, not all genetic variants BRCA1 and BRCA2 VUS in the MENA region. We searched
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have known clinical significance. Variants of unknown several electronic databases, including PubMed, Google
significance (VUS) are genetic mutations that have yet to Scholar, and Embase, to identify relevant studies published
be classified as either benign or pathogenic. 10 up to early 2024. The study was conducted in accordance
The identification of VUS within the BRCA1 and BRCA2 with the Preferred Reporting Items for Systematic Reviews
presents a critical challenge in both BC research and and Meta-Analyses (PRISMA) guidelines (Figure 1).
clinical practice. VUS can cause profound uncertainty and 2.2. Search strategy
emotional distress for both patients and their families. In
addition, healthcare professionals face complex decisions A combination of Medical Subject Heading terms and
regarding the clinical management of BC cases with VUS keywords was used to identify relevant studies. The search
findings, a task further complicated by the evolving nature terms included “BRCA1,” “BRCA2,” “variant of uncertain
of genetic research. 11 significance,” “VUS,” “Middle East,” “North Africa,”
“MENA region,” and the names of specific countries. We
Therefore, it is essential to reclassify these variants also manually searched the reference lists of identified
to redefine their clinical significance, ensuring accurate articles for additional studies. Original research articles
genetic counseling. This process guides individuals and their were selected from Morocco, Algeria, Tunisia, Egypt,
families in making informed decisions about screening, Palestine, Jordan, Saudi Arabia, Yemen, Oman, United
preventive measures, and treatment. Furthermore, Arab Emirates, Qatar, Bahrain, Kuwait, Iraq, Lebanon,
reclassification contributes to the development of Cyprus, and Turkey. No studies on BRCA VUS were found
personalized medicine, enabling tailored interventions for Mauritania, Libya, or Syria, and therefore, no data are
based on an individual’s unique genetic profile. 12 available for these countries. Studies were included if they

However, the reclassification of VUS in BRCA1 and met the following criteria: (i) conducted in the MENA
BRCA2 is a complex process that requires analysis of multiple region, (ii) focused on the role of BRCA1 and/or BRCA2
lines of evidence. Clinical, genetic, and population-based in BC and/or OC, (iii) reported the prevalence of BRCA1
data are all important considerations in the classification and BRCA2 VUS in individuals with a family or personal

Volume 9 Issue 1 (2025) 17 doi: 10.36922/ejmo.5800