Genetics and Genetic Testing in Pancreatic Cancer

Gastroenterology. 2015 Oct;149(5):1252-1264.e4. doi: 10.1053/j.gastro.2015.07.057. Epub 2015 Aug 6.


Genetic testing of germline DNA is used in patients suspected of being at risk of pancreatic ductal adenocarcinoma (PDAC) to better define the individual's risk and to determine the mechanism of risk. A high genetic risk increases the pretest probability that a biomarker of early cancer is a true positive and warrants further investigation. The highest PDAC risk is generally associated with a hereditary predisposition. However, the majority of PDAC results from complex, progressive gene-environment interactions that currently fall outside the traditional risk models. Over many years, the combination of inflammation, exposure to DNA-damaging toxins, and failed DNA repair promote the accumulation of somatic mutations in pancreatic cells; PDAC risk is further increased by already present oncogenic germline mutations. Predictive models and new technologies are needed to classify patients into more accurate and mechanistic PDAC risk categories that can be linked to improved surveillance and preventative strategies.

Keywords: Familial Pancreatic Cancer; Genetic Testing; Hereditary Breast and Ovarian Cancer Syndrome; Hereditary Pancreatitis.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / metabolism
  • DNA Repair
  • Environment*
  • Genetic Predisposition to Disease
  • Genetic Testing / methods*
  • Germ-Line Mutation
  • Humans
  • Inflammation / genetics
  • Mutation*
  • Risk Factors


  • Biomarkers, Tumor