Germline mutation prevalence in individuals with pancreatic cancer and a history of previous malignancy

Cancer. 2018 Apr 15;124(8):1691-1700. doi: 10.1002/cncr.31242. Epub 2018 Jan 23.


Background: Approximately 10% of pancreatic adenocarcinoma (PC) cases are attributed to hereditary causes. Individuals with PC and a personal history of another cancer associated with hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS) may be more likely to carry germline mutations.

Methods: Participants with PC and a history of cancer were selected from a pancreatic disease registry. Of 1296 individuals with PC, 149 had a relevant history of cancer. If banked DNA was available, a multigene panel was performed for individuals who had not 1) previously had a mutation identified through clinical testing or 2) undergone clinical multigene panel testing with no mutations detected.

Results: Twenty-two of 124 individuals with PC and another HBOC- or LS-related cancer who underwent genetic testing had a mutation identified in a PC susceptibility gene (18%). If prostate cancer is excluded, the mutation prevalence increased to 23% (21/93). Mutation carriers were more likely to have more than 1 previous cancer diagnosis (P = .001), to have had clinical genetic testing (P = .001), and to meet National Comprehensive Cancer Network (NCCN) genetic testing criteria (P < .001). Approximately 23% of mutation carriers did not meet NCCN HBOC or LS testing guidelines based on their personal cancer history and reported cancer history in first-degree relatives.

Conclusion: At least 18% of individuals with PC and a personal history of other HBOC- or LS-related cancers carry mutations in a PC susceptibility gene based on our data, suggesting that criteria for genetic testing in individuals with PC should include consideration of previous cancer history. Cancer 2018;124:1691-700. © 2018 American Cancer Society.

Keywords: Lynch syndrome; genetic testing; germline mutation; hereditary breast and ovarian cancer syndrome; pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Hereditary Breast and Ovarian Cancer Syndrome / genetics
  • Humans
  • Male
  • Medical History Taking
  • Middle Aged
  • Neoplasms, Second Primary / genetics*
  • Pancreatic Neoplasms / genetics*
  • Young Adult


  • Biomarkers, Tumor

Supplementary concepts

  • Pancreatic Carcinoma