Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history

Kari G. Chaffee, Ann L. Oberg, Robert R. McWilliams, Neil Majithia, Brian A. Allen, John Kidd, Nanda Singh, Anne Renee Hartman, Richard J. Wenstrup, Gloria M. Petersen

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


PurposePanel-based genetic testing has identified increasing numbers of patients with pancreatic ductal adenocarcinoma (PDAC) who carry germ-line mutations. However, small sample sizes or number of genes evaluated limit prevalence estimates of these mutations. We estimated prevalence of mutations in PDAC patients with positive family history.MethodsWe sequenced 25 cancer susceptibility genes in lymphocyte DNA from 302 PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreatic Research Registry. Kindreds containing at least two first-degree relatives with PDAC met criteria for familial pancreatic cancer (FPC), while the remaining were familial, but not FPC.ResultsThirty-six patients (12%) carried at least one deleterious mutation in one of 11 genes. Of FPC patients, 25/185 (14%) were carriers, while 11/117 (9%) non-FPC patients with family history were carriers. Deleterious mutations (n) identified in PDAC patients were BRCA2 (11), ATM (8), CDKN2A (4), CHEK2 (4), MUTYH/MYH (3 heterozygotes, not biallelic), BRCA1 (2), and 1 each in BARD1, MSH2, NBN, PALB2, and PMS2. Novel mutations were found in ATM, BARD1, and PMS2.ConclusionMultiple susceptibility gene testing in PDAC patients with family history of pancreatic cancer is warranted regardless of FPC status and will inform genetic risk counseling for families.

Original languageEnglish (US)
Pages (from-to)119-127
Number of pages9
JournalGenetics in Medicine
Issue number1
StatePublished - Jan 1 2018


  • familial pancreatic cancer (FPC)
  • pancreatic ductal adenocarcinoma (PDAC)
  • pathogenic variant (PV)
  • variant of uncertain significance (VUS)

ASJC Scopus subject areas

  • Genetics(clinical)


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