BRCA mutation screening and patterns among high-risk Lebanese subjects.

BACKGROUND

Previous studies have suggested that the prevalence of and mutations in the Lebanese population is low despite the observation that the median age of breast cancer diagnosis is significantly lower than European and North American populations. We aimed at reviewing the rates and patterns of mutations found in individuals referred to the medical genetics unit at the American University of Beirut. We also evaluated the performance of clinical prediction tools.

METHODS

We retrospectively reviewed the cases of all individuals undergoing mutation testing from April 2011 to May 2016. To put our findings in to context, we conducted a literature review of the most recently published data from the region.

RESULTS

Two-hundred eighty one individuals were referred for testing. The prevalence of mutated or genes were 6 and 1.4% respectively. Three mutations accounted for 54% of the pathogenic mutations found. The c.131G > T mutation was found among 5/17 (29%) unrelated subjects with mutation and is unique to the Lebanese and Palestinian populations. For patients tested between 2014 and 2016, all patients positive for mutations fit the NCCN guidelines for mutation screening. The Manchester Score failed to predict pathogenic mutations.

CONCLUSION

The c.131G > T mutation can be considered a founder mutation in the Lebanese population detected among 5/17 (29%) of individuals diagnosed with a mutation in and among 7/269 families in this cohort. On review of recently published data regarding the landscape of mutations in the Middle East and North Africa, each region appears to have a unique spectrum of mutations.