Inflammation-Related Risk Factors for Pancreatic Cancer - A Systematic Review with a Focus on Early Onset Cases

Abstract

Background and aims: Chronic inflammation has been recognized as a key contributor to pancreatic cancer development. The impact of inflammation-related risk factors on early-onset pancreatic cancer remains understudied; thus, we aim to summarize evidence on inflammation-related risk factors associated with pancreatic cancer development, focusing on early-onset pancreatic ductal adenocarcinoma (PDAC). Methods: This systematic review follows PRISMA guidelines. A comprehensive literature search was performed across PubMed, Scopus, and Web of Science, using MeSH terms and Boolean operators to identify studies examining inflammation-related risk factors for PDAC. Publications were screened against predefined eligibility criteria and the quality of evidence was assessed using the GRADE framework, which was conducted independently by two reviewers. Results: This systematic review analyzed 45 studies examining inflammation-related risk factors for pancreatic cancer, focusing on ductal adenocarcinoma. Strong and consistent associations were observed between obesity, smoking, and chronic inflammation with an increased risk of PDAC, with some studies highlighting potential synergistic effects. Diet-related inflammation showed a weaker and less consistent association. Notably, obesity and smoking emerged as significant risk factors, particularly in early-onset PDAC. Conclusion: Inflammation-related risk factors play a significant role in the development of PDAC, including cases occurring in younger populations. These findings underscore the complex etiology of PDAC and the interplay between modifiable and clinical factors. Further research is essential to refine these associations and elucidate the underlying mechanisms, particularly early-onset PDAC, to inform targeted prevention strategies and improve risk stratification.