Familial Pancreatic Cancer, Hereditary Pancreatic Cancer, Pancreatic Cancer, Adult
Conditions
Keywords
Screening, Pancreatic cancer, High risk pancreatic cancer, Hereditary pancreatic cancer, Familial pancreatic cancer, miRNA pancreatic cancer
Brief summary
Background: Pancreatic cancer (PC) is an aggressive cancer with only a 7% 5-year survival rate, primarily due to late-stage diagnosis. In Spain, its incidence is rising, and by 2030, it is expected to become the second leading cause of cancer-related death worldwide. Approximately 3% of PCs occur in the context of hereditary pancreatic cancer (HPC) predisposition syndromes. Studies have shown that up to 40% of genetic mutations associated with PC in individuals under 60 years old would not have been identified using traditional clinical criteria for genetic testing. Presymptomatic genetic testing is recommended for relatives of patients with hereditary syndromes to identify those at higher risk of PC and to include them in screening programs to alter the natural history of the disease. However, there is no robust evidence supporting the best tool for early diagnosis in at-risk individuals. Currently, screening relies on endoscopic ultrasound or magnetic resonance imaging, which yield suboptimal results. Aims: By studying the clinical, molecular, and genetic characteristics of PC patients and their families, this project aims to identify factors conferring higher PC risk and to adopt preventive measures while evaluating the efficacy of current screening strategies. Additionally, the project includes a traslational subproject to identify new hereditary genes associated with increased PC risk and novel molecules (biomarkers, specifically miRNAs) with diagnostic potential. These biomarkers could serve as non-invasive tools to identify individuals at increased risk of PC through blood tests, enabling preventive measures or early diagnosis. Given the low incidence of PC (albeit with high mortality), collaborative studies are essential to achieve meaningful results. The current project represents the first Spanish multicenter population-based registry for PC, integrating clinical data and biological sample collection alongside a control group. Its goal is to prevent PC and foster collaboration between basic research and clinical application in Spain within a proven collaborative framework. Establishing the best strategy to detect high-risk individuals for PC within the general population. Identifying new PC risk genes to expand the identification of at-risk individuals. Determining effective prevention strategies for high-risk individuals. Creating a national network, PREVENPANC, for collaborative PC research, including the collection of biological samples (blood) from all enrolled patients.
Interventions
GENETICMultigene panel
Germline Genetic Testing: Germline genetic testing will be performed on all patients with pancreatic cancer (PC) using a custom multigene panel. This panel includes 25 candidate genetic variants of interest and 13 clinically recognized genes associated with a higher risk of PC. DNA Extraction: Germline DNA will be extracted from peripheral blood samples using the QIAamp DNA Blood Kit (Qiagen, Redwood City, CA, USA) following the manufacturer's instructions. The concentration of double-stranded DNA will be measured using a fluorometric method (Qubit, Thermo Fisher Scientific).
DIAGNOSTIC_TESTOther
1. Characterization of Suspected Pancreatic Cancer Lesions: Characterization of suspected pancreatic cancer (PC) lesions identified by endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) in patients undergoing screening since 2014. This includes lesion type (solid or cystic), rapid cyst growth exceeding 4 mm per year, location, size, potential assessment of resectability, lobulocentric parenchymal atrophy, and Wirsung duct dilation. Clinically relevant suspected lesions will be defined as solid lesions, intraductal papillary mucinous neoplasms (IPMN), cystic lesions ≥10 mm, and cystic lesions with mural nodules. 2. Determination of CA 19-9 and Glycated Hemoglobin: Measurement of CA 19-9 levels and glycated hemoglobin (HbA1c) as part of the diagnostic and monitoring process.
DIAGNOSTIC_TESTmiRNA measurement in blood
Analysis of miRNA Expression in plasma: The expression of circulating miRNAs (in plasma) will be analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The signature includes two miRNAs (miR-33a-3p and miR-320a) combined with CA 19-9.
GENETICGeneration of 3D Pancreatic Organoids
Generation of 3D Pancreatic Organoids for Complementary Analyses: 3D pancreatic organoids will be generated for complementary analyses involving in vitro functional studies to evaluate the pathogenicity of novel genes (selected based on the results of the multigene panel). These organoids will be developed from surgical samples obtained from five patients undergoing surgery as part of clinical care.
Sponsors
Hospital Universitario de Canarias
Hospital Universitario Marqués de Valdecilla
Hospital Universitario Ramon y Cajal
Hospital de Cruces
Hospital Universitario de Puerta de Hierro
Clinica Universidad de Navarra, Universidad de Navarra
Complexo Hospitalario de Ourense
Hospital Clinic of Barcelona
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Patients with a recent diagnosis of pancreatic cancer in the general population. * High-risk individuals under follow-up in high-risk clinics (hereditary syndromes, familial pancreatic cancer).
Exclusion criteria
* Patients under 18 years old. * Patients who have undergone treatment for pancreatic cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of Pancreatic Cancer Risk Groups within the General Population | Until March 2026 | \*Clinical Protocol: \- Identify the factors and risk groups globally associated with pancreatic cancer (PC). |
| Evaluate Screening Strategies in High-Risk Individuals | Until October 2026 | \*Clinical Protocol: -Identify specific risk factors associated with pancreatic cancer (PC) in families with familial pancreatic cancer (FPC) or hereditary pancreatic cancer (HPC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Identification of Pancreatic Cancer Risk Groups within the General Population | Until March 2026 | \*Clinical Protocol: \- Establish the most effective strategy for identifying individuals with a hereditary predisposition to PC. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Establish a Spanish Multicenter Network for Collaborative Research on Pancreatic Cancer Prevention in Our Setting (PREVENPANC) | November 2025 | Create a Cohort with Clinical Information and Biological Samples: Establish a cohort comprising individuals with and without pancreatic pathology as a control group for future projects within the PREVENPANC network. |
Contacts
Primary ContactIrina Luzko
Backup ContactLeticia Moreira, PhD
Outcome results
None listed