Pancreatic Adenocarcinoma Associated With a Germline RAD51C Mutation

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality in the United States, with a 5-year survival of ∼10%-13%. Although 5%-10% of PDAC cases arise from pathogenic germline variants in cancer-predisposition genes, association with RAD51C remains exceedingly rare, with only one prior case reported. We describe a 64-year-old woman who presented with progressive epigastric pain and was found to have a hypermetabolic pancreatic head mass with markedly elevated CA 19-9. Endoscopic biopsy confirmed pancreatic adenocarcinoma (MSI-stable, HER2-negative), staged as cT2N0M0. Comprehensive germline testing identified a pathogenic RAD51C mutation. The patient declined treatment and genetic counseling, electing for palliative care. RAD51C plays a critical role in homologous recombination DNA repair, and its loss may confer sensitivity to platinum-based chemotherapy and poly (ADP-ribose) polymerase inhibitors. This case represents only the second reported RAD51C-associated PDAC and reinforces the importance of universal germline testing to identify hereditary risk and guide therapeutic strategies.