Abstract 247P
Background
Recent advances in detection of germline pathogenic variants (PVs) in BRCA1/2 genes allowed a deeper understanding of the BRCA-related cancer risk. Several studies showed a significant heterogeneity in the prevalence of PVs across different populations. The development of new population-based genetic approaches may help to detect the 50% more BRCA-carriers than those identified by conventional clinical and familial criteria, as already shown in other studies. Because little is known about this in Sicilian population, our study was aimed at investigating the prevalence and geographic distribution of inherited BRCA1/2 PVs in families from this specific geographical area of Southern Italy.
Methods
We retrospectively collected and analyzed all clinical information of 1,346 hereditary breast and/or ovarian cancer patients genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis at University Hospital Policlinico “P. Giaccone” of Palermo from January 1999 to October 2019.
Results
102 BRCA-positive subjects carried a BRCA1 PV, 96 harboured a BRCA2 PV, and 2 showed simultaneous presence of PVs in both genes. Thirty PVs were more frequently observed in the Sicilian population, but only some of these showed a specific territorial prevalence, unlike other Italian and European regions. This difference could be attributed to the genetic heterogeneity of the Sicilian people and its historical background due to the crucial geographical location of Sicily in the centre of Mediterranean Sea, crossroads of several cultures. Therefore, hereditary breast and ovarian cancers in Sicily could be predominantly due to BRCA1/2 PVs different from those usually detected in other geographical areas of Italy and Europe.
Conclusions
Our investigation led us to hypothesize that a higher prevalence of some germline BRCA PVs in Sicily could be a population-specific genetic signature. Population-based genetic approaches, in the future, could help to increase the BRCA carrier detection rates and maximize prevention strategies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University Hospital Policlinico “P. Giaccone” of Palermo.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.