Genetic and Circulating Biomarker Data Improve Risk Prediction for Pancreatic Cancer in the General Population

Cancer Epidemiol Biomarkers Prev. 2020 May;29(5):999-1008. doi: 10.1158/1055-9965.EPI-19-1389. Epub 2020 Apr 22.


Background: Pancreatic cancer is the third leading cause of cancer death in the United States, and 80% of patients present with advanced, incurable disease. Risk markers for pancreatic cancer have been characterized, but combined models are not used clinically to identify individuals at high risk for the disease.

Methods: Within a nested case-control study of 500 pancreatic cancer cases diagnosed after blood collection and 1,091 matched controls enrolled in four U.S. prospective cohorts, we characterized absolute risk models that included clinical factors (e.g., body mass index, history of diabetes), germline genetic polymorphisms, and circulating biomarkers.

Results: Model discrimination showed an area under ROC curve of 0.62 via cross-validation. Our final integrated model identified 3.7% of men and 2.6% of women who had at least 3 times greater than average risk in the ensuing 10 years. Individuals within the top risk percentile had a 4% risk of developing pancreatic cancer by age 80 years and 2% 10-year risk at age 70 years.

Conclusions: Risk models that include established clinical, genetic, and circulating factors improved disease discrimination over models using clinical factors alone.

Impact: Absolute risk models for pancreatic cancer may help identify individuals in the general population appropriate for disease interception.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Humans
  • Male
  • Middle Aged
  • Models, Statistical*
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / epidemiology*
  • Pancreatic Neoplasms / genetics
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Risk Assessment / methods
  • Risk Assessment / statistics & numerical data
  • Risk Factors
  • United States / epidemiology


  • Biomarkers, Tumor

Grant support