LAUSR

BACKGROUD The frequency and significance of the germline variants in DNA damage repair genes still need to be elucidated in patients with sporadic pancreatic ductal adenocarcinoma (PDAC). Our purpose was to determine whether germline variants in DNA damage repair genes were associated with survival of patients with sporadic PDAC. STUDY DESIGN We retrospectively identified 854 patients with sporadic PDAC with germline DNA sequenced in targeted 22 DNA damage repair genes by next-generation sequencing. Outcomes were compared in terms of clinicopathologic features, disease-free survival (DFS) and overall survival (OS). RESULTS Nineteen patients had deleterious mutations; 103 had variant(s) of unknown significance (VUS). Germline DNA damage repair deleterious variant carriers had superior DFS (median, 19.1 months vs. 11.9 months, p=0.012) and OS (median, 29.7 months vs. 20.2 months, p=0.034) as compared with wild-type patients. Germline DNA damage repair VUS variant carriers also had superior DFS when compared with wild-type patients. In subgroup analysis, this improved survival was limited to patients receiving adjuvant chemotherapy, deleterious variant carriers vs. wild-type patients DFS (median, 36.3 months vs. 13.1 months, p=0.006) and OS (median, 43.7 months vs. 24.3 months, p=0.045), VUS variant carriers vs. wild-type patients DFS (16.5 months vs. 13.1 months, p=0.007). CONCLUSION Having a deleterious variant in a DNA damage repair gene is associated with improved survival after resection and adjuvant chemotherapy for pancreatic ductal adenocarcinoma.