Causal Exposures in Pancreatic Cancer Incidence: Insights From Mendelian Randomization Studies Publisher



Mohamadkhani A¹ ; Ghanbari R³ ; Shakeri R⁴ ; Mohammadkhani MA⁵ ; Pourshams A¹
Source: JGH Open Published:2025

Abstract

Aim: Pancreatic cancer, marked by its high lethality and poor 5-year survival rate, requires a thorough understanding of its risk factors and etiological mechanisms. In this review, we collected the latest findings from Mendelian randomization (MR) studies to identify potential causal factors for pancreatic cancer. Method and Results: The present analysis encompasses MR studies on the gut and oral microbiomes, non-malignant phenotypes, blood metabolites, immune cells, and chronic inflammation. Specific gut and oral microbiome species have been identified as potential causal factors for pancreatic cancer, some with protective effects, and others increasing the risk. The review also highlights causal associations between obesity, type 2 diabetes, and pancreatic cancer, as well as the impact of blood metabolites and immune cell phenotypes on disease risk. Additionally, it investigates the causal effects of inflammatory bowel disease, showing a significant risk increase associated with Crohn's disease. Conclusion: These insights emphasize the need for interdisciplinary research and personalized medicine to enhance prevention and treatment strategies for pancreatic cancer. © 2025 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.