Germline genetic profiling utilizing multigene panel testing in Jordanian patients with pancreatic cancer: a comprehensive cancer center experience.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths worldwide. Between 5% and 10% of PDACs are attributable to inherited genetic alterations, identification of which may enhance targeted screening and inform treatment decisions. Data on germline variants among Arab patients with PDAC are lacking. METHODS: This prospective study included adult patients with PDAC treated at King Hussein Cancer Center in Amman, Jordan. Patients underwent multigene panel (MGP) testing using either standard or investigational panels. Cascade family testing was offered to relatives of patients with positive results. Germline testing results were classified as benign (negative), pathogenic/likely pathogenic (P/LP) (positive) or variants of uncertain significance (VUS). RESULTS: A total of 211 patients, all of whom had PDAC as their first cancer diagnosis upon enrollment, were included in the analysis. The median age at diagnosis was 59 years, and 63.0% were males. In total, 22 (10.4%) patients had positive mutations; 14 (6.6%) as pathogenic/likely pathogenic (P/LP) variants, mostly in BRCA2 (n = 8), while 8 others (3.8%) had increased risk allele in APC. Other variants identified included ATM, CFTR, CHEK2, BRCA1, and MSH6. Half (n = 11, 50.0%) of patients with P/LP variants or APC increased risk allele communicated results with their relatives; 18 (69.2%) of 26 relatives tested had positive results. CONCLUSIONS: Our study underscores the relevance of PDAC germline genetic testing among the Arab population. Given its clinical implications for screening and management, universal testing should be advocated. Communicating test results with at-risk relatives, despite its importance, remains suboptimal and warrants further investigation.