Pathogenic germline mutations prevalence in Saudi patients with pancreatic ductal adenocarcinoma.

Abstract

538 Background: While the majority of pancreatic ductal adenocarcinoma(PDAC) cases are sporadic, about 10% related to familial and hereditary component. Multiple studies have shown that germline genetic testing regardless of family history for patients with PDCA is feasible and more likely to identify the carrier of pathogenic mutations. There is no data about the prevalence of pathogenic germline mutations in Saudi population. We aimed to study the prevalence of these mutations in Saudi patient patients with PDAC regardless of the family history of cancer. Methods: By using our cancer genetics database, we analyzed all the confirmed cases of PDAC who were referred to the cancer genetic clinic at King Abdulaziz medical city in Riyadh, Kingdom of Saudi Arabia. Since November 2018, a comprehensive hereditary cancer gene panel (including 70 genes) is offered to all referred PDAC cases regardless of their family history of cancer after obtaining a genetic counselling assessment and an informed consent. Results: Between November 2018 and August 2021, a total of 88 patients with PDAC cases have been tested. The median age was 60 and the majority of patients were males (n=56, 64%). Most of the patients had stage IV disease (n=75, 85.23%). The genetic result was available for 86 patients. Pathogenic variant(PVs) was reported in 8.1% (n=7), variant of uncertain significance (VUSs) was reported in 15% (n=13) while no mutation reported in the rest of the patients. The PVs reported were BRCA2 (n=4), BRIP1 (n=1), PMS1(n=1) and MRE11 (n=1). All the carriers of the PVs had no documented family history of breast, ovarian or pancreatic cancers at the time of genetic counselling. Conclusions: This study confirms the importance of genetic testing in all patients with PDAC regardless of the family history. This is in line with previous studies from other populations. This is the first study from Saudi patients with PDAC and to the best of our knowledge, the first study in Arab population.