BReast CAncer gene (BRCA): snapshot of the Middle East
Editorial Commentary on Targeting the DNA Damaging Pathway: PARPi and Beyond

BReast CAncer gene (BRCA): snapshot of the Middle East

Omalkhair Abulkhair1, Nagi S. El Saghir2

1Department of Oncology, Specialized Medical Center, Riyadh, Saudi Arabia; 2Division of Hematology-Oncology, Breast Center of Excellence, American University of Beirut Medical Center, Beirut, Lebanon

Correspondence to: Omalkhair Abulkhair, MD. Department of Oncology, Specialized Medical Center, P.O. Box 66548, Riyadh 11586, Saudi Arabia. Email: omal_danah@hotmail.com; omalkhair.abdullah@smc.com.sa.

Submitted Sep 11, 2019. Accepted for publication Feb 03, 2021.

doi: 10.21037/cco-19-204

Background

Breast cancer (BC) is the most common cancer in the world, accounting for approximately 23% of all cancers that affect females worldwide, and remains the most common cause of mortality in women globally (1). About 5–10% of all BC cases (2) and more than 23% of all ovarian cancers (3) are thought to be hereditary. Hereditary breast and ovarian cancer is commonly caused by an autosomal dominant BReast CAncer gene (BRCA) germ line mutation which causes a higher than normal incidence of ovarian and BC in genetically related families (4).

Women in the Arab world are diagnosed with BC at more advanced stages, with the incidence rates in this region increasing over the last three decades (5-10).

BRCA data

BRCA gene mutations have been identified as the most commonly linked germ-line mutations (11). Pathogenic mutations in both BRCA1 and BRCA2 increase the risk of developing BC up to 85% and ovarian cancer up to 54% during woman’s lifetime (12). BRCA mutation occurrences are known to differ between populations and ethnic groups. Some studies also describe significant differences in the spectrum of BRCA1 compared with BRCA2 mutations, and in the BRCA1/2 variants of uncertain significance (VUS) (13,14). For instance, from a sample of 46,276 women of non-Ashkenazi Jewish ancestry, females with African ancestry had the highest prevalence of VUS [16.5% vs. 5.7% Western European; odds ratio (OR): 3.2, 2.8–3.7] (13), while BRCA2 mutations were reported to be more frequent than those of BRCA1 in the Asian population (15). Furthermore, population-specific mutations have also been described among Ashkenazi Jews (16) and patients of Spanish ancestry (17).

Founder BRCA1 and BRCA2 mutations have also been found in several European populations in Austria, Slovenia, Italy, France, Spain, Portugal, Belgium, the Netherlands Germany, the Czech Republic, Slovakia, Hungary, Greece, Cyprus, Denmark, Sweden, Norway, Finland, Iceland, the United Kingdom, Ireland, Poland, Latvia, Lithuania, Estonia, Belarus, and Russia (18).

In Saudi Arabian women, BC is ranked first among all cancers, accounting for 27% of all newly diagnosed malignancies. While the majority of BC cases are sporadic, familial susceptibility to BC constitutes 25% of all cases (16).

Although the population in Saudi Arabia is largely homogeneous and consanguinity is very common, especially in the central, eastern, and southern regions of the country, the prevalence of BRCA1 and BRCA2 mutations and the characteristics of BC have not been extensively studied. Available data are conflicting and inconclusive, as they are based on retrospective analyses from small heterogeneous groups of Saudi and non-Saudi patients (19-24).

In this paper, we present a snapshot of the BRCA studies that have been conducted in Arab countries in the Middle East. The BRCA studies examined included those involving both BRCA1 and BRCA2. Table 1 shows the summary of studies included in this paper.

Table 1

BRCA mutations among breast and/or ovarian cancer patients in Arab countries

Author Year Country Sample size Age at diagnosis (range or mean) Test type Mutation type
Bu 2016 Saudi Arabia 818 41.9 PCR, CS/SS4, and TCS Deleterious
El Saghir 2015 Lebanon 250 40.8 MLPA Deleterious, VUS
Abdel-Razeq 2018 Jordan 100 22–75 BART Deleterious, suspected-deleterious
Bujassoum 2017 Qatar 82 <50 MLPA Deleterious
Jalkh 2012 Lebanon 72 41 Fluorescent DS Deleterious, VUS
Abulkhair 2018 Saudi Arabia 310 – PCR Deleterious
Ibrahim 2010 Egypt 60 43.5 SSCP, HAC Deleterious
Khalil 2018 Syria 50 36 PCR Deleterious

BART, comprehensive BRACAnalysis and BRACAnalysis Rearrangement Test; PCR, polymerase chain reaction; CS, capture sequencing; SS, sanger sequencing; TCS, targeted capture sequencing; MLPA, multiple ligation-dependent probe amplification; SSCP, single-strand conformation polymorphism assay; HAC, heteroduplex assay confirmation; DS, direct sequencing; VUS, variants of uncertain significance.

Six countries with varying incidence rates and types of BRCA mutations were included: Saudi Arabia, Lebanon, Jordan, Qatar, Egypt, and Syria. The sample sizes ranged between 50 and 800 patients and the mean age at diagnosis ranged from 22 to 75 years. The type of testing employed varied and included multiple techniques. Mutation types were mostly deleterious.

There was a variability in the prevalence of BRCA mutations in patients at high risk of having hereditary BC between 5.6% to 20% between different countries of the Arab world (11,19,25,26). These differences might be explained by either biological differences in BRCA gene prevalence (27) or differences in the age at onset in the study population (28,29). Studies have also suggested that there is a variation of BRCA prevalence among different ethnicities (16) while others found that the prevalence of these mutations is the same across different ethnicities (13). Family history of breast or ovarian cancer emerged as a significantly strong predictor for BRCA gene mutations (30).

Conclusions

Understanding population-specific BRCA gene distributions is critical, as this knowledge can be helpful in devising appropriate risk-assessment strategies to reduce the risk of cancer emergence and developing cost-effective strategies for genetic testing for BRCA mutations (24).

High-quality large-sample studies are necessary to better understand and recognize the impact of BRCA gene mutations and their role in breast and ovarian cancer incidence, risk and prognosis, surveillance, management, and outcome in this part of the world where cancer incidence is steadily increasing.

Acknowledgments

The authors would like to thank Ms. Sheryl Ann Abdukahil and Ms. Donabel Bigtas-Castro for their outstanding editorial support.

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editor (Shaheenah Dawood) for the series “Targeting the DNA Damaging Pathway: PARPi and Beyond” published in Chinese Clinical Oncology. The article has undergone external peer review.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cco-19-204). The series “Targeting the DNA Damaging Pathway: PARPi and Beyond” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Cite this article as: Abulkhair O, El Saghir NS. BReast CAncer gene (BRCA): snapshot of the Middle East. Chin Clin Oncol 2021;10(5):51. doi: 10.21037/cco-19-204

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