Identification of high-risk germline variants for the development of pancreatic cancer: Common characteristics and potential guidance to screening guidelines

Pancreatology. 2022 Sep;22(6):719-729. doi: 10.1016/j.pan.2022.05.005. Epub 2022 May 27.

Abstract

Pancreatic cancer (PC) is a product of a variety of environmental and genetic factors. Recent work has highlighted the influence of hereditary syndromes on pancreatic cancer incidence. The purpose of this review is to identify the high-risk syndromes, common variants, and risks associated with PC. The study also elucidates common characteristics of patients with these mutations, which is used to recommend potential changes to current screening protocols for greater screening efficacy. We analyzed 8 syndromes and their respective variants: Hereditary Breast and Ovarian Cancer (BRCA1/2), Familial Atypical Multiple Mole Melanoma Syndrome (CDKN2A), Peutz-Jeghers Syndrome (STK11), Lynch Syndrome (PMS2, MLH1, MSH2, MSH6, EPCAM), Ataxia Telangiectasia (ATM), Li-Fraumeni Syndrome (TP53), Fanconi Anemia (PALB2), and Hereditary Pancreatitis (PRSS1, SPINK1, CFTR). Of 587 studies evaluated, 79 studies fit into our inclusion criteria. Information from each study was analyzed to draw conclusions on these variants as well as their association with pancreatic cancer. Information from this review is intended to improve precision medicine and improve criteria for screening.

Publication types

  • Review

MeSH terms

  • Early Detection of Cancer / methods
  • Genetic Predisposition to Disease
  • Germ Cells
  • Germ-Line Mutation*
  • Humans
  • Pancreatic Neoplasms* / diagnosis
  • Pancreatic Neoplasms* / epidemiology
  • Pancreatic Neoplasms* / genetics
  • Syndrome
  • Trypsin Inhibitor, Kazal Pancreatic / genetics

Substances

  • SPINK1 protein, human
  • Trypsin Inhibitor, Kazal Pancreatic