COMMON GENETIC MUTATIONS BETWEEN TYPE 2 DIABETES AND PANCREATIC CANCER: A SYSTEMATIC REVIEW OF THE LITERATURE

Abstract

INTRODUCTION: Pancreatic cancer (PC) is one of the most aggressive and lethal neoplasms. Among the main risk factors is diabetes mellitus (DM), which significantly increases its probability and development. Studies indicate that patients with DM have a higher risk due to genetic mutations common to both conditions, which affect both the cell cycle and metabolism, promoting oncogenesis and insulin resistance. METHODS: This is a literature review on the genetic mutations shared between PC and DM and current therapeutic approaches, with a focus on gene therapy. The search was performed in the PubMed Advanced database, using the descriptors (DECS/MeSH): "pancreatic cancer", "diabetes mellitus" and "genetic therapy". A total of 15 articles were selected for detailed analysis. RESULTS: The review identified significant genetic mutations associated with both PC and DM. Among the most relevant genes are KRAS, CDKN2A, TP53, CFTR and SPINK1. In terms of therapeutic approaches, gene editing with CRISPR/Cas9, the use of viral vectors for the delivery of therapeutic genes, and the modulation of microRNAs stand out. DISCUSSION: The interrelationship between PC and DM is profound and goes beyond a simple coexistence of conditions. Mutations in genes such as KRAS, TP53, and CDKN2A not only drive oncogenesis but also affect glucose metabolism, contributing to insulin resistance. Gene therapy, especially CRISPR/Cas9 editing, appears as a promising solution, offering a more specific and less invasive alternative compared to conventional treatments, such as chemotherapy and radiotherapy. CONCLUSION: The study highlights the importance of understanding the common genetic mutations between PC and DM, with emphasis on the KRAS, CDKN2A, TP53, CFTR, and SPINK1 genes. Gene therapy, especially through gene editing with CRISPR/Cas9, shows promise for correcting these mutations. However, more studies are needed to ensure the safety and efficacy of these techniques in humans, especially about possible off-target effects and immune response.