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Prospective Study of Germline Genetic Testing in Incident Cases of Pancreatic Adenocarcinom

Specialty Areas:
Date: August 3, 2018
Authors:
A. James Moser, Allan Tsung, Amer Zureikat, Arlene Colvin, Beth Dudley, Cynthia Lim, Emily Dalton, Erkut Borazanci, Eve Karloski, Herbert Zeh, Holly Laduca, James Lee, James Ohr, Jill Dolinsky, Jill Krejdovsky, John Rhee, Kenneth Lee, Kim DeLeonardis, Lindsey Stobie, Mary Helen Black, Mary Linton B. Peters, Melissa Hogg, Nadine Tung M, Nathan Bahary, Randall Brand, Virginia Speare, Weijing Sun
Journal: Cancer
Collaborators:
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Abstract

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.