Dose-response relationship of cadmium and pancreatic cancer risk: a meta-analysis

Abstract

Cadmium (Cd), a group 1 carcinogen, is linked to the development of pancreatic cancer. Not well-defined is the dose-response relationship between Cd and cancer development.This study investigated the relationship between Cd exposure and the risk of pancreatic cancer through a meta-analysis focusing on pooled relative risk (RR), biomarker comparisons and dose-response relationships.This meta-analysis adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and applied the PECO (population, exposure, comparator and outcomes) framework. Systematic searches of key databases, including PubMed, Cochrane Library, Web of Science, EMBASE, ScienceDirect and ProQuest, were carried out without language restrictions. Studies that met the predefined PECO criteria were chosen, extracting data on effect estimates such as HRs, ORs, RRs and Cd biomarker concentrations. Analyses involved pooled RRs, standardised mean differences for biomarker comparisons and dose-response relationships, using random-effects meta-analysis and meta-regression. Statistical procedures were performed on R V.4.3.0.Cd exposure was significantly associated with an increased risk of pancreatic cancer, with a pooled RR of 1.42 (95% CI=1.16 to 1.73). Subgroup analyses confirmed this association in both occupationally and non-occupationally exposed individuals. Dose-response analyses further revealed that higher Cd biomarker levels correlated with greater pancreatic cancer risk (lnRR coefficient=0.610, p=0.035).Cd exposure is associated with an increased risk of pancreatic cancer, with a dose-response relationship and elevated biomarker levels in cases. Cd exposure is a modifiable risk factor for pancreatic cancer, meriting further investigation.

Keywords: Cadmium; Gastroenterology; Meta-analysis; Occupational Health; Public health.

Figure 1. Flowchart of study selection. N, number of studies; n, number of study groups; PECO, population, exposure, comparator and outcomes.

Figure 2. Forest plot of the pooled effect of cadmium exposure on pancreatic cancer risk, by sex.

Figure 3. Meta-regression of the association between cadmium (Cd) exposure and pancreatic cancer risk. The plot shows the dose-response relationship between cadmium concentration (μg/g) and the natural log-transformed relative risk (lnRR) for pancreatic cancer, based on a random-effects meta-regression model. The solid line represents the fitted trend, with the shaded area indicating the 95% CI. Each point represents a study-specific group, defined by biomarker type (urine, pancreatic tissue or toenail). Cadmium concentrations reflect values reported within individual studies, and the lnRR represents the estimated change in risk per 1 µg/g increase in exposure. Note: Some elevated lnRR values at near-zero exposure levels reflect comparisons to reference groups with extremely low background Cd levels, which may exaggerate relative differences even when absolute exposures are low.