ABSTRACT
Background and Objectives: Pancreatic cancer (PC) is the third cause of cancer-related deaths. Early detection and interception of premalignant pancreatic lesions represent a promising strategy to improve outcomes. We evaluated risk factors of focal pancreatic lesions (FPLs) in asymptomatic individuals at hereditary high risk for PC. Methods: This is an observational single-institution cohort study conducted over a period of 5 years. Surveillance was performed through imaging studies (EUS or magnetic resonance imaging/magnetic resonance cholangiopancreatography) and serum biomarkers. We collected demographic characteristics and used univariate and multivariate logistic regression models to evaluate associations between potential risk factors and odd ratios (ORs) for FPL development. Results: A total of 205 patients completed baseline screening. Patients were followed up to 53 months. We detected FPL in 37 patients (18%) at baseline; 2 patients had lesions progression during follow-up period, 1 of them to PC. Furthermore, 13 patients developed new FPLs during the follow-up period. Univariate and multivariate analyses revealed that new-onset diabetes (NOD) is strongly associated with the presence of FPL (OR, 10.94 [95% confidence interval, 3.01-51.79; P < 0.001]; OR, 9.98 [95% confidence interval, 2.15-46.33; P = 0.003]). Follow-up data analysis revealed that NOD is also predictive of lesions progression or development of new lesions during screening (26.7% vs. 2.6%; P = 0.005). Conclusions: In a PC high-risk cohort, NOD is significantly associated with presence of FPL at baseline and predictive of lesions progression or new lesions during surveillance.
Subject(s)
Carcinoma, Pancreatic Ductal/diagnosis , Early Detection of Cancer , Pancreatic Neoplasms/diagnosis , Peutz-Jeghers Syndrome/diagnosis , Carcinoma, Pancreatic Ductal/complications , Carcinoma, Pancreatic Ductal/therapy , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Pancreas/diagnostic imaging , Pancreas/pathology , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/therapy , Peutz-Jeghers Syndrome/complications , Risk FactorsABSTRACT
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.
Subject(s)
Carcinoma, Pancreatic Ductal/genetics , Genetic Predisposition to Disease , Neoplastic Syndromes, Hereditary/epidemiology , Pancreatic Neoplasms/genetics , Adult , Age Factors , Age of Onset , Aged , Aged, 80 and over , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Carcinoma, Pancreatic Ductal/mortality , Cohort Studies , DNA Mismatch Repair/genetics , DNA Mutational Analysis , Female , Genetic Counseling , Humans , Male , Medical History Taking , Middle Aged , Neoplastic Syndromes, Hereditary/diagnosis , Neoplastic Syndromes, Hereditary/genetics , Pancreatic Neoplasms/mortality , Prevalence , Risk Factors , Survival AnalysisABSTRACT
It is well known that pancreatic ductal adenocarcinoma has a high mortality rate. Despite progress in understanding the biology and genetic basis of this disease, life expectancy has changed minimally in the last 50 years. This article highlights the importance of screening patients at high risk for developing pancreatic cancer and reviews current methods as well as methods in development for pancreatic cancer early detection and surveillance.
