Hereditary Pancreatic Cancer: Genetic Risk, Surveillance Strategies, and Therapeutic Implications

Area of Science:

• Oncology
• Genetics
• Cancer Research

Background:

• Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a poor prognosis, often diagnosed late.
• Approximately 5-10% of PDAC cases are linked to inherited cancer susceptibility syndromes.

Purpose of the Study:

• To review the genetic landscape of hereditary pancreatic cancer (HPC) and familial pancreatic cancer (FPC).
• To summarize evidence on germline pathogenic variants (PGVs), their prevalence, penetrance, and clinical relevance.
• To discuss challenges in identifying at-risk individuals, genetic testing recommendations, and surveillance strategies.

Main Methods:

• Literature review of hereditary cancer syndromes and susceptibility genes.
• Summary of current evidence on PGVs in PDAC.
• Analysis of genetic testing approaches and surveillance programs for high-risk individuals.

Main Results:

• Germline variants in DNA repair and cell-cycle genes (e.g., BRCA1/2, CDKN2A, TP53) contribute to PDAC risk.
• Evidence on PGV prevalence, penetrance, and clinical impact is summarized.
• Challenges in risk identification and implementation of genetic testing and surveillance are highlighted.

Conclusions:

• Understanding the genetic basis of hereditary PDAC is crucial for early detection and risk management.
• Germline genetic testing and tailored surveillance are essential for high-risk individuals.
• Therapeutic strategies for PDAC may be informed by inherited genetic alterations, particularly in DNA repair-deficient tumors.