Prospective Study of Germline Genetic Testing in Incident Cases of Pancreatic Adenocarcinoma.

Brand R1, Borazanci E2, Speare V3, Dudley B1, Karloski E1, Peters MLB4, Stobie L4, Bahary N1, Zeh H5, Zureikat A5, Hogg M5, Lee K5, Tsung A5, Rhee J1, Ohr J1, Sun W6, Lee J1, Moser AJ4, DeLeonardis K4, Krejdovsky J4, Dalton E3, LaDuca H3, Dolinsky J3, Colvin A2, Lim C2, Black MH3, Tung N4.

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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. Cancer 2018;000:000-000. © 2018 American Cancer Society.