Metabolic Dysfunction and Related Dietary Exposures in Relation to Pancreatic Cancer Risk: A Review of the Evidence

Vollständiger Abstract

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Pancreatic cancer is a highly lethal malignancy with an increasing global incidence. Although metabolic dysfunction has been implicated in pancreatic cancer risk, the strength and consistency of evidence across different metabolic traits remain uncertain. Evidence for dietary exposures related to metabolic regulation is also less clearly established. This umbrella review synthesised evidence from systematic reviews, meta-analyses, and umbrella reviews evaluating metabolic dysfunction and related dietary exposures in relation to pancreatic cancer risk. A systematic search of PubMed, Web of Science, and PROSPERO identified reviews published between 1 January 2021 and 1 February 2026. Seventeen reviews met the inclusion criteria. The primary search focused on metabolic dysfunction. Dietary exposures identified during the screening process were retained as a secondary evidence domain when they were considered relevant to glycaemic regulation, insulin response, adiposity, or wider metabolic health. Primary-study overlap was slight, with an overall corrected covered area (CCA) of 1.59% and weighted corrected covered area (wCCA) of 1.40%; within the principal evidence domains of adiposity-related exposures and metabolic dysfunction, the CCA and wCCA were 1.15% and 1.81%, respectively. Metabolic dysfunction demonstrated the strongest and most consistent associations with pancreatic cancer risk. Metabolic syndrome, diabetes mellitus, hyperglycaemia, and abdominal obesity were graded as probable evidence. Hyperglycaemia showed the strongest component-level association (RR = 1.55, 95% CI: 1.42–1.70), while diabetes mellitus was consistently associated with increased risk across both cohort and case–control studies. Abdominal obesity, assessed using waist circumference and waist-to-hip ratio, was also positively associated with risk. General obesity, prediabetes, and reduced HDL cholesterol were graded as limited/suggestive evidence, whereas hypertriglyceridaemia was graded as limited/no conclusion. Related dietary exposures generally showed weaker and less consistent associations, with no exposure supported by convincing evidence. Overall, pancreatic cancer risk was more consistently associated with systemic metabolic dysfunction, particularly impaired glucose regulation, diabetes, metabolic syndrome, and abdominal adiposity, than with the related dietary exposures examined. However, the evidence remains predominantly observational and does not establish causality.