High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early-Onset Pancreatic Cancer
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Abstract
Introduction: We aimed to determine the prevalence and landscape of germline mutations among patients with young-onset pancreatic ductal adenocarcinoma (PDAC) as well as their influence in prognosis. Methods: Patients from two cohorts were studied, the high-risk cohort (HRC), which included 584 PDAC patients who received genetic counseling at The University of Texas MD Anderson Cancer Center, and a general cohort (GC) with 233 metastatic PDAC patients. We defined germline DNA sequencing on 13 known pancreatic cancer susceptibility genes. The prevalence and landscape of mutations were determined, and clinical characteristics including survival were analyzed. Results: A total of 409 patients underwent genetic testing (277 from HRC and 132 from GC). As expected, the HRC had higher prevalence of germline mutations compared with the GC: 17.3% versus 6.81%. The most common mutations in both cohorts were in BRCA1/2 and mismatch-repair (MMR) genes. Patients younger than 60 years old had significantly higher prevalence of germline mutations in both the HRC [odds ratios (OR), 1.93 ± 1.03–3.70, P = 0.039] and GC (4.78 ± 1.10–32.95, P = 0.036). Furthermore, PDAC patients with germline mutations in the GC had better overall survival than patients without mutations (HR, 0.44; 95% CI of HR, 0.25–0.76, P = 0.030). Discussion: Germline mutations are highly prevalent in patients with PDAC of early onset and can be predictive of better outcomes. Considering emerging screening strategies for relatives carrying susceptibility genes as well as impact on therapy choices, genetic counseling and testing should be encouraged in PDAC patients, particularly those of young onset. Cancer Prev Res; 11(11); 679–86. ©2018 AACR.
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Deleterious variants have been reported in about 5-10% of patients with apparently sporadic pancreatic cancer.
“Deleterious variants have also been reported in ~5–10% of patients with apparently sporadic pancreatic cancer.”
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- Authors
- Bannon, S. A., Montiel, M. F., Goldstein, J. B., Dong, W., Mork, M. E., Borras, E., Hasanov, M., Varadhachary, G. R., Maitra, A., Katz, M. H., Feng, L., Futreal, A., Fogelman, D. R., Vilar, E., & McAllister, F.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- 2Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.
- The University of Texas Health Science Center at Houston (US)
- 8Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
- Corresponding author
- McAllister, Florencia
- ORCID
- Venue
- Cancer Prevention Research
- Published
- 2018-11-01
- Volume
- 11
- Issue
- 11
- Pages
- 679-686
- ISSN
- 1940-6207 (ISSN-L)
- 1940-6215
- PMC
- PMC6343472
- OpenAlex
- W2894708272
- Cited by
- 40
- References
- 26
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 12 · 2023: 6 · 2022: 8 · 2021: 3 · 2020: 2 · 2019: 5 · 2018: 1
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Prevention Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- HHS | NIH | National Cancer Institute (NCI) (K12CA088084-16A1)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- germline mutations, hereditary cancer, BRCA1/2, mismatch repair genes, overall survival, genetic counseling, genetic testing, young adults, cancer susceptibility
- MeSH terms
- Adult, Age Factors, Aged, Aged, 80 and over, DNA Mutational Analysis, Female, Genetic Counseling, Humans, Male, Medical History Taking, Middle Aged, Neoplastic Syndromes, Hereditary, Pancreatic Neoplasms, Risk Factors, Cohort Studies, Prevalence, Survival Analysis, Age of Onset, BRCA1 Protein, Genetic Predisposition to Disease, Carcinoma, Pancreatic Ductal, BRCA2 Protein, DNA Mismatch Repair
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