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.

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.

1. Population-Based Cohort:

   Prospective inclusion of all patients diagnosed with pancreatic cancer (PC) over a 12-month period at participating centers, paired with a control group of individuals without known pancreatic pathology. Controls will be matched by age, sex, and self-identified gender.

2. Retrospective Cohort (Individuals from Families with Familial Pancreatic Cancer or Hereditary Pancreatic Cancer):

Observational multicenter study with retrospective inclusion of all individuals from families with familial pancreatic cancer (FPC) or hereditary pancreatic cancer (HPC) who have been under follow-up from 2014 to the present in the High Risk Digestive Cancer Clinics of the participating centers. Peripheral blood samples (serum, plasma, and DNA) from most of these individuals are currently available in biobank storage.