Variants of unknown significance in BRCA1 and BRCA2 among breast cancer patients in Middle Eastern and North African populations: A systematic review

Abstract

Breast cancer (BC) is a growing global health challenge, particularly in low- and middle-income countries. Variants of unknown significance (VUS) in BC genes, BRCA1 and BRCA2, complicate genetic counseling and treatment decisions, emphasizing the need for reclassification. This systematic review aimed to determine the spectrum of VUS in BRCA1 and BRCA2 among BC patients from the Middle East and North Africa (MENA) region and to evaluate the current understanding and potential reclassification of these variants. A comprehensive search was conducted across electronic databases, including PubMed, Google Scholar, and Embase, for studies published up to early 2024. The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria encompassed studies conducted in the MENA region that focused on BRCA1 and/or BRCA2 in BC and/or ovarian cancer, reported on VUS prevalence, and analyzed coding regions or known mutations. Data extraction was performed using a standardized form, and VUS was reviewed through multiple databases. The review identified 34 eligible studies, with a slight predominance of Middle Eastern studies (n = 18) over North African (n = 16) studies. On reclassification using the ClinVar database, 26% of the VUS were reclassified as benign or likely benign, 34.5% presented conflicting interpretations of pathogenicity, 2% were reclassified as pathogenic or likely pathogenic, and 16.5% remained uncertain. The remaining variants were either not reported or lacked classification. The included studies covered multiple countries in the MENA region, providing insights into the prevalence and characteristics of BRCA1 and BRCA2 VUS in BC patients. The continuous reclassification of VUS is essential for enhancing genetic counseling for BC patients, as it helps clarify the clinical implications of these variants. The findings contribute to understanding the genetic factors in BC susceptibility and may inform clinical practices in genetic counseling and risk assessment in this population.

Keywords

BRCA1 / BRCA2 / Variants of uncertain significance / Breast cancer / Middle East and North Africa / Genetic susceptibility

Funding

None.

Conflict of interest

The authors declare that they have no competing interests.

References

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