Cadmium Exposure and Risk of Pancreatic Cancer: A Systematic Review and Meta-Analysis
Clinical Snapshot
PICO Framework
| P — Population | Adult humans with cadmium exposure (occupational, environmental, or biomarker-measured) across multiple study designs and geographic regions |
| I — Intervention | Cadmium exposure — occupational (industrial/mining), environmental (dietary/ambient), and biomarker-based (urinary cadmium, blood/serum cadmium) |
| C — Comparator | Unexposed or lowest-exposure reference groups within included studies |
| O — Outcomes | Pancreatic cancer incidence or mortality (relative risk as pooled effect measure) |
Bottom Line
This PRISMA-compliant systematic review and meta-analysis of 18 studies reports a statistically significant association between cadmium exposure and pancreatic cancer risk (pooled RR 1.69, 95% CI 1.28–2.22), with the most consistent signal in occupational exposure settings (RR 1.38, 95% CI 1.19–1.61). The findings are hypothesis-generating and reinforce the biological plausibility of cadmium as a pancreatic carcinogen, likely mediated through oxidative stress, DNA damage, and interference with zinc-dependent tumour suppressor pathways. However, several methodological limitations temper confidence in these estimates. The absence of a linear dose-response relationship weakens causal inference under Bradford Hill criteria. Significant publication bias was detected in the urinary cadmium subgroup. No GRADE assessment was performed, heterogeneity statistics were not reported, and residual confounding from co-exposures — particularly tobacco smoke, which is both a cadmium source and an independent pancreatic carcinogen — cannot be excluded. The higher RR in case-control versus cohort studies further raises concern for recall and selection bias. For Australian clinicians and occupational health practitioners, this evidence supports vigilance regarding cadmium exposure minimisation in high-risk industries, but is insufficient to justify new pancreatic cancer screening protocols. Further prospective cohort studies with rigorous confounder adjustment are needed.
Key Findings
P Value: Not reported for primary pooled estimate; Egger's test P = 0.045 for urinary cadmium publication bias
Effect Size: Overall pooled RR = 1.69; Occupational exposure subgroup RR = 1.38
Primary Outcome: Pancreatic cancer incidence or mortality associated with cadmium exposure
Nnt Or Sensitivity: No NNT calculable from available data; dose-response meta-regression did not demonstrate a statistically significant linear trend across cadmium exposure levels
Confidence Interval: Overall: 95% CI 1.28–2.22; Occupational: 95% CI 1.19–1.61
Clinical Application
Urinary cadmium is a validated biomarker of cumulative cadmium body burden and is measurable in occupational health surveillance settings. However, no evidence-based cadmium-specific pancreatic cancer screening protocol currently exists, and the absence of a dose-response relationship limits the ability to define actionable exposure thresholds. Primary prevention through occupational exposure minimisation remains the most feasible intervention. In Australia, cadmium exposure is regulated under Safe Work Australia's Workplace Exposure Standards (WES), with an 8-hour time-weighted average of 0.01 mg/m³ for cadmium and cadmium compounds. Relevant industries include mining (particularly zinc-lead operations in Queensland and New South Wales), battery recycling, and phosphate fertiliser manufacturing. The TGA does not currently list cadmium-related pancreatic cancer risk in any approved product information. RACGP guidelines do not include cadmium biomarker testing in routine preventive health assessments. Dietary cadmium exposure in Australia occurs primarily through cereals, vegetables, and seafood; Food Standards Australia New Zealand (FSANZ) monitors cadmium levels in the food supply. This meta-analysis provides epidemiological support for maintaining and strengthening existing occupational exposure controls, but does not yet provide sufficient evidence to justify new clinical screening recommendations in the Australian context. Adults with occupational cadmium exposure (battery manufacturing, metal smelting, electroplating, pigment production, phosphate fertiliser industries) and potentially the general population with elevated dietary or environmental cadmium exposure. Men appear to be at higher relative risk than women based on subgroup analyses.
Abstract
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.
References
- 1.Seyyedsalehi, M. S., Ciaccio, L., Marra, R. F., & Boffetta, P. (2026). Cadmium exposure and risk of pancreatic cancer: A systematic review and meta-analysis. La Medicina del lavoro. https://doi.org/10.23749/mdl.2026.19093
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