Prospective study of germline genetic testing in incident cases of pancreatic adenocarcinoma

Randall Brand, Erkut Borazanci, Virginia Speare, Beth Dudley, Eve Karloski, Mary Linton B. Peters, Lindsey Stobie, Nathan Bahary, Herbert Zeh, Amer Zureikat, Melissa Hogg, Kenneth Lee, Allan Tsung, John Rhee, James Ohr, Weijing Sun, James Lee, A. James Moser, Kim DeLeonardis, Jill KrejdovskyEmily Dalton, Holly LaDuca, Jill Dolinsky, Arlene Colvin, Cynthia Lim, Mary Helen Black, Nadine Tung

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


BACKGROUND: The objective of this study was to investigate the prevalence of pathogenic germline variants (PGVs) in 32 cancer susceptibility genes in individuals with newly diagnosed pancreatic ductal adenocarcinoma (PDAC). A key secondary objective was to evaluate how often PGVs would have been undetected with existing genetic testing criteria. METHODS: From May 2016 through May 2017, this multicenter cohort study enrolled consecutive patients aged 18 to 89 years with histologically confirmed PDAC diagnosed within the previous 12 weeks. Demographics, medical histories, and 3-generation pedigrees were collected from participants who provided samples for germline DNA analysis. RESULTS: Four hundred nineteen patients were deemed eligible, 302 were enrolled, and 298 were included in the final cohort. Clinically actionable variants were reported in 29 PDAC patients (9.7%), with 23 (7.7%) having a PGV associated with an increased risk for PDAC. Six of 23 individuals (26%) with PDAC-associated gene mutations did not meet currently established genetic testing criteria. According to guideline-based genetic testing, only 11 of the 23 PGVs (48%) in known PDAC genes would have been detected. Six additional patients (2%) had PGVs associated with an increased risk for other cancers. CONCLUSIONS: These findings support the significant prevalence of PGVs associated with PDAC and the limitations of current paradigms for selecting patients for genetic testing, and they thereby lend support for universal germline multigene genetic testing in this population.

Original languageEnglish (US)
Pages (from-to)3520-3527
Number of pages8
Issue number17
StatePublished - Sep 1 2018
Externally publishedYes


  • genetic susceptibility
  • genetic testing
  • germline mutation
  • hereditary cancer syndromes
  • pancreatic ductal adenocarcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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