DNA Damage and Repair in Pancreatic Cancer-The Latest Findings.

Pancreatic cancer is one of the most common cancers of the gastrointestinal tract, alongside stomach and colon cancers, yet remains among the least studied. Due to its non-specific symptoms, late diagnosis, and limited treatment options, it is associated with a poor prognosis and high mortality. Major risk factors for pancreatic cancer include smoking, alcohol consumption, pancreatitis, obesity, and type 2 diabetes. These environmental factors can damage DNA through various mechanisms and, if not properly repaired, may initiate carcinogenesis. DNA repair is one of the key mechanisms in cancer prevention. It has been suggested that impaired DNA repair may contribute to the development and progression of pancreatic cancer. The aim of this review is to highlight the link between environmental factors, DNA damage and DNA repair in pancreatic cancer. Environmental exposures can trigger a cascade of molecular events, including ROS (reactive oxygen species) overproduction, oxidative stress, insulin resistance, hyperglycemia, and inflammation, that lead to DNA damage. Additionally, up to 25% of patients with PDAC (pancreatic ductal adenocarcinoma) carry mutations in DDR (DNA damage response) genes, and only 5% of all cases are hereditary. Therefore, increased DNA damage combined with disturbances in DDR creates a condition accelerating pancreatic cancer progression. Further research should focus on DDR pathways as potential targets for screening and therapy. Such an approach could significantly improve early diagnosis and treatment outcomes. Moreover, uncovering the mechanisms linking pancreatic cancer aggressiveness with DNA repair deficiencies may lead to the development of specific biomarkers, enabling early detection and potentially improving patient survival.