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

J Surg Oncol. 2023 Aug;128(2):289-294. doi: 10.1002/jso.27289. Epub 2023 Apr 21.

Abstract

Background and objectives: Modest 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.

Methods: All patients undergoing prospective screening at a single institution from 2013 to 2019 were reviewed.

Results: Of 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).

Conclusion: In 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.

Keywords: germline mutations; hereditary pancreatic cancer; intraductal papillary mucinous neoplasms; pancreatic cancer screening.

MeSH terms

  • Carcinoma, Pancreatic Ductal* / diagnosis
  • Carcinoma, Pancreatic Ductal* / epidemiology
  • Carcinoma, Pancreatic Ductal* / genetics
  • Early Detection of Cancer
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Humans
  • Pancreatic Intraductal Neoplasms* / genetics
  • Pancreatic Intraductal Neoplasms* / pathology
  • Pancreatic Neoplasms* / diagnosis
  • Pancreatic Neoplasms* / epidemiology
  • Pancreatic Neoplasms* / genetics
  • Prospective Studies