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Cancer Prev Res (Phila). 2018 Nov;11(11):679-686. doi: 10.1158/1940-6207.CAPR-18-0014. Epub 2018 Oct 1.

High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early-Onset Pancreatic Cancer.

Author information

1
Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
2
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3
Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
4
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
5
Internal Medicine Department, The University of Texas Health Science Center at Houston, Houston, Texas.
6
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
7
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
8
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
9
Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas. fmcallister@mdanderson.org.
#
Contributed equally

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.

PMID:
30274973
PMCID:
PMC6343472
[Available on 2019-11-01]
DOI:
10.1158/1940-6207.CAPR-18-0014

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