Association Between Dietary Total Fat and Cholesterol Intake and Pancreatic Cancer Risk: A Dose-Response...

Background: Pancreatic cancer (PC) is a highly lethal malignancy with a poor prognosis. Dietary total fat and cholesterol intake have been suggested as potential modifiable risk factors, but the evidence remains inconsistent. This study aimed to systematically evaluate the association between dietary total fat and cholesterol intake and PC risk. Methods: A comprehensive literature search was conducted in PubMed, Scopus, Google Scholar, and Web of Science from database inception to May 2026. Cohort and case-control studies reporting relative risks (RRs), odds ratios (ORs), or hazard ratios (HRs) for the association between dietary total fat or cholesterol intake and PC risk were included. Pooled effect size (ES) and 95% confidence intervals (CIs) were calculated using random-effects models. Results: Twenty-five studies (17 case-control and 8 cohort studies) were included, most of which were of high quality. Cohort studies showed no association of dietary cholesterol (ES: 1.02; 95% CI: 0.87-1.20) or total fat intake (ES: 1.00; 95% CI: 0.84-1.20) with PC risk. In case-control studies, high cholesterol intake was associated with increased PC risk (ES: 1.63; 95% CI: 1.32-2.01), whereas total fat intake was not (ES: 1.18; 95% CI: 0.85-1.65). In cohort studies, dose-response analyses showed no significant associations between cholesterol or total fat intake and PC. In case-control studies, each 100 mg/day increase in cholesterol intake was associated with a 13% higher risk of PC, whereas no significant dose-response association was observed for total fat intake. Subgroup and sensitivity analyses supported these findings, and no publication bias was detected. Conclusions: Dietary cholesterol and total fat intake were not associated with PC risk in cohort studies, whereas case-control studies suggested a positive association between cholesterol intake and PC risk. Further prospective studies are needed to clarify these associations.