BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: A PACGENE study

David B. Zhen, Kari G. Rabe, Steven Gallinger, Sapna Syngal, Ann G. Schwartz, Michael G. Goggins, Ralph H. Hruban, Michele L. Cote, Robert R. McWilliams, Nicholas J. Roberts, Lisa A. Cannon-Albright, Donghui Li, Kelsey Moyes, Richard J. Wenstrup, Anne Renee Hartman, Daniela Seminara, Alison P. Klein, Gloria M. Petersen

Research output: Contribution to journalArticlepeer-review

137 Scopus citations


Purpose:Familial pancreatic cancer kindreds contain at least two affected first-degree relatives. Comprehensive data are needed to assist clinical risk assessment and genetic testing.Methods:Germ-line DNA samples from 727 unrelated probands with positive family history (521 met criteria for familial pancreatic cancer) were tested in compliance with the Clinical Laboratory Improvement Amendments for mutations in BRCA1 and BRCA2 (including analysis of deletions and rearrangements), PALB2, and CDKN2A. We compared prevalence of deleterious mutations between familial pancreatic cancer probands and nonfamilial pancreatic cancer probands (kindreds containing at least two affected biological relatives, but not first-degree relatives). We also examined the impact of family history on breast and ovarian cancers and melanoma.Results:Prevalence of deleterious mutations (excluding variants of unknown significance) among familial pancreatic cancer probands was: BRCA1, 1.2%; BRCA2, 3.7%; PALB2, 0.6%; and CDKN2A, 2.5%. Four novel deleterious mutations were detected. Familial pancreatic cancer probands carry more mutations in the four genes (8.0%) than nonfamilial pancreatic cancer probands (3.5%) (odds ratio: 2.40; 95% confidence interval: 1.06-5.44; P = 0.03). The probability of testing positive for deleterious mutations in any of the four genes ranges up to 10.4%, depending on family history of cancers. BRCA2 and CDKN2A account for the majority of mutations in familial pancreatic cancer.Conclusion:Genetic testing of multiple relevant genes in probands with a positive family history is warranted, particularly for familial pancreatic cancer.Genet Med 17 7, 569-577.

Original languageEnglish (US)
Pages (from-to)569-577
Number of pages9
JournalGenetics in Medicine
Issue number7
StatePublished - Jul 2 2015


  • BRCA1
  • BRCA2
  • CDKN2A
  • PALB2
  • familial pancreatic cancer

ASJC Scopus subject areas

  • Genetics(clinical)


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