BRCA mutation screening and patterns among high-risk Lebanese subjects

Area of Science:

• Genetics and Genomics
• Oncology
• Population Health

Background:

• Previous studies indicated low BRCA1/2 mutation prevalence in Lebanon, contrasting with an earlier median age of breast cancer diagnosis compared to Western populations.
• The study aimed to review BRCA1/2 mutation rates and patterns in Lebanese individuals referred for genetic testing.
• Evaluation of clinical prediction tools for BRCA mutations was also a key objective.

Purpose of the Study:

• To determine the prevalence and specific types of BRCA1 and BRCA2 mutations in the Lebanese population.
• To identify potential founder mutations within the Lebanese demographic.
• To assess the utility of clinical prediction tools like the Manchester Score for identifying individuals with BRCA mutations.

Main Methods:

• Retrospective review of 281 individuals who underwent BRCA mutation testing between April 2011 and May 2016.
• Literature review of recent regional data on BRCA mutations to contextualize findings.
• Analysis of mutation prevalence, specific mutation types, and performance of prediction tools.

Main Results:

• BRCA1 and BRCA2 mutation prevalence was 6% and 1.4%, respectively.
• The BRCA1 c.131G>T mutation was identified in 29% of individuals with BRCA1 mutations and is unique to Lebanese and Palestinian populations, suggesting a founder effect.
• All mutation-positive patients tested between 2014-2016 met NCCN guidelines; the Manchester Score was ineffective in predicting mutations.

Conclusions:

• The BRCA1 c.131G>T mutation is likely a founder mutation in the Lebanese population.
• The Middle East and North Africa region exhibits a unique spectrum of BRCA mutations.
• Clinical prediction tools require further validation for diverse populations.