Cadmium Exposure and Risk of Pancreatic Cancer: A Systematic Review and Meta-Analysis

Introduction: Pancreatic cancer is a highly lethal malignancy with poor prognosis and limited treatment options. Environmental exposures, particularly to heavy metals such as cadmium, may contribute to its etiology. This systematic review and meta-analysis evaluated the association between cadmium exposure from different sources and pancreatic cancer incidence or mortality. Methods: Following PRISMA guidelines, we searched PubMed, EMBASE, and Scopus. Eighteen studies comprising 20 risk estimates were included. Random-effects meta-analyses were conducted overall and stratified by exposure source, gender, region, study design, and outcome. Dose-response relationships were assessed using meta-regression of cadmium exposure measures. Publication bias was evaluated using funnel plots and Egger's test. Results: Overall, cadmium exposure was associated with an increased risk of pancreatic cancer [relative risk (RR) = 1.69, 95% confidence interval (CI): 1.28-2.22]. Occupational exposure showed the most consistent association (RR = 1.38, 95% CI: 1.19-1.61), followed by urinary and blood/serum biomarkers. Risk was higher in men than in women, and in case-control than in cohort studies. Dose-response analysis did not reveal a linear trend. There was limited evidence of publication bias overall, though some asymmetry was observed for urinary cadmium studies (P = 0.045). Conclusion: Cadmium exposure was associated with pancreatic cancer risk, particularly in occupational and biomarker-based studies. While findings support a potential causal link, heterogeneity, residual confounding, and limited dose-response data necessitate cautious interpretation.