Prospective study of germline genetic testing in incident cases of pancreatic adenocarcinoma
| Autor: | Jill Krejdovsky, Mary Helen Black, James Ohr, Holly LaDuca, Mary Linton B. Peters, A. James Moser, Arlene Colvin, Nadine Tung, Eve Karloski, Jill S. Dolinsky, Weijing Sun, Virginia Speare, John C. Rhee, Nathan Bahary, Kim DeLeonardis, Melissa E. Hogg, Amer H. Zureikat, Kenneth H. Lee, James Cheng Yen Lee, Randall E. Brand, Beth Dudley, Allan Tsung, Herbert J. Zeh, Lindsey Stobie, Erkut Borazanci, Cynthia Lim, Emily Dalton |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty education.field_of_study endocrine system diseases medicine.diagnostic_test business.industry Population Gene mutation 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Germline mutation 030220 oncology & carcinogenesis Internal medicine Cohort medicine Genetic predisposition business Prospective cohort study education Genetic testing Cohort study |
| Zdroj: | Cancer. 124:3520-3527 |
| ISSN: | 0008-543X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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