2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-The Status of Germline Variants of Unknown Significance in Minorities: Middle Eastern Patients with HBOC

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The study conducted at the American University of Beirut aimed to assess the status of germline testing in Middle Eastern patients at high risk for hereditary breast and ovarian cancer (HBOC). The interpretation of variants of unknown significance (VUS) in genetic testing poses a major challenge for specialists and causes psychological burden for patients. While VUS constitute around 5-10% of detected variants in Western populations, there is limited data on VUS in Arab and Middle Eastern countries.<br /><br />The study reviewed germline testing results from 2010 to 2019 for patients from Lebanon, Syria, Palestine, Jordan, and Iraq. A total of 245 patients were included, with 210 having breast cancer, 31 with ovarian cancer, and a few others with breast plus prostate or ovarian cancer. Among these patients, 14% had pathogenic or likely pathogenic variants (P/LP), and 77% had VUS.<br /><br />The analysis revealed that Middle Eastern patients had a higher percentage and number of VUS compared to Western populations. Additionally, there was a high proportion of variants that were not reported in public databases, highlighting the lack of resources allocated to genetic testing in the Middle East. The study also identified four variants that were reclassified, with two BRCA2 variants and one CHEK2 variant being upgraded to pathogenic or likely pathogenic.<br /><br />The findings emphasize the importance of genetic counseling before and after testing to help patients understand the implications and uncertainties of VUS. It also calls for more comprehensive genetic testing databases to improve the interpretation of VUS in diverse populations.<br /><br />In summary, the study conducted at the American University of Beirut examined germline testing results in Middle Eastern patients at high risk for HBOC. The findings showed a high percentage of VUS and a lack of reported variants in public databases. The study highlights the challenges of interpreting VUS and the need for improved genetic counseling and databases for diverse populations.

Asset Subtitle

Presenting Author - Nada Assaf, MD; Co-Author - Hassan Diab, MS; Co-Author - Nagi Saghir, MD;

Meta Tag

Genetic Testing

Genetic Diversity

Cancer Syndromes

Co-Author Nagi Saghir, MD

Co-Author Hassan Diab, MS

Presenting Author Nada Assaf, MD

Keywords

germline testing

Middle Eastern patients

high risk

hereditary breast and ovarian cancer

variants of unknown significance

genetic testing

psychological burden

pathogenic variants

likely pathogenic variants

public databases