Patients with deleterious germline mutations: A heterogeneous population for pancreatic cancer screening?

Abstract

AbstractBackground and ObjectivesModest data exist on the benefits of screening and surveillance for pancreatic cancer (PC) in high‐risk individuals. Intraductal papillary mucinous neoplasms (IPMN) are known precursors to PC. We hypothesized that patients with high‐risk deleterious germline mutations have a higher prevalence of IPMN.MethodsAll patients undergoing prospective screening at a single institution from 2013 to 2019 were reviewed.ResultsOf 1166 patients screened, 358 (31%) possessed germline mutations and/or family history of PC (mutations n = 201/358, 56%, family history n = 226/358, 63%) (median follow‐up 2.7 years). IPMN was found in 127 patients (35.5%). The prevalence of IPMN in mutation carriers (18%) was higher than in the general population (p < 0.01). Germline mutation was an independent predictor of IPMN (odds ratio [OR] = 3.2; p < 0.01), while family history was not (p = 0.22). IPMN prevalence was distributed unevenly between mutation types (67%‐Peutz‐Jeghers; 43%‐HNPCC, 24%‐BRCA2; 17%‐ATM; 9%‐BRCA1; 0%‐CDKN2A and PALB2).ConclusionIn this series, 18% of mutation carriers harbored IPMN, higher than the general population. Germline mutation, but not a family history of PC, was independently associated with IPMN. This prevalence varied across mutation subtypes, suggesting not all mutation carriers develop precancerous lesions. Genetic testing for patients with a positive family history may improve screening modalities for this high‐risk population.