Table of Contents
Background on Pancreatic Cancer and Environmental Risk Factors
Pancreatic cancer remains one of the most lethal malignancies globally, presenting significant challenges in terms of diagnosis and treatment. Characterized by a poor prognosis and limited therapeutic options, it is the seventh leading cause of cancer-related deaths worldwide, with a five-year survival rate of less than 10% (Soleimani et al., 2025). This dismal outlook can be attributed to the disease’s tendency to be diagnosed at advanced stages, coupled with its inherent resistance to conventional therapies.
A growing body of evidence suggests that environmental factors, particularly exposure to heavy metals like cadmium, may play a pivotal role in the development and progression of pancreatic cancer. Cadmium is classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC), indicating sufficient evidence of its carcinogenicity in humans. Chronic exposure to cadmium has been linked to various health issues, including kidney damage and bone fragility, raising concerns about its potential role in carcinogenesis (Soleimani et al., 2025). Given its toxic profile, understanding the implications of cadmium exposure on pancreatic cancer risk is crucial for public health and cancer prevention strategies.
The Role of Cadmium in Cancer Development and Progression
Cadmium is a naturally occurring heavy metal that has been widely used in industrial processes, such as mining, smelting, and battery manufacturing. Human exposure primarily occurs through contaminated food, tobacco smoke, and occupational hazards in industrial settings. Once absorbed, cadmium tends to accumulate in organs, including the liver, kidneys, and pancreas, with a biological half-life exceeding ten years, making chronic exposure a significant public health concern (Soleimani et al., 2025).
Mechanistically, cadmium contributes to cancer development through multiple pathways. It generates reactive oxygen species (ROS), which can lead to oxidative stress, DNA damage, and mutations. Additionally, cadmium can induce chronic inflammation, interfere with DNA repair mechanisms, and disrupt normal cell signaling pathways, promoting uncontrolled cell proliferation—hallmarks of cancer development (Soleimani et al., 2025). While links between cadmium exposure and other cancers, such as lung and prostate cancer, have been well-established, its specific association with pancreatic cancer has remained less clear, with epidemiological studies yielding conflicting results.
The pancreas is particularly susceptible to oxidative stress and inflammatory damage due to its unique cellular composition and microenvironment. The inflammatory response induced by cadmium may exacerbate pancreatic injury, leading to the initiation and progression of pancreatic cancer. However, variability in study designs and exposure measurements has complicated the understanding of this association (Soleimani et al., 2025).
Methodology of Systematic Review and Meta-Analysis
To systematically evaluate the relationship between cadmium exposure and pancreatic cancer risk, a comprehensive literature search was conducted across multiple electronic databases, including PubMed, Scopus, Web of Science, and Embase. The search encompassed studies published until May 1, 2024, focusing on human observational studies that assessed cadmium exposure and reported on pancreatic cancer incidence.
Inclusion criteria for the studies were as follows:
- Studies that assessed cadmium exposure through environmental or occupational sources.
- Studies that reported sufficient data to calculate risk estimates, such as odds ratios (OR) or hazard ratios (HR) with 95% confidence intervals (CIs).
- Peer-reviewed articles published in any language, with a focus on human populations.
Exclusion criteria included studies lacking adequate data on cadmium exposure, reviews, editorials, case reports, or animal studies, and studies where cadmium was measured indirectly or where confounding heavy metals were not adequately controlled.
Following the initial search, titles and abstracts were screened independently by two reviewers against the inclusion and exclusion criteria. Full texts of potentially relevant studies were obtained for further evaluation. Data extraction was standardized, capturing key variables such as study design, sample size, geographic location, population characteristics, exposure assessment methods, and risk estimates. The Joanna Briggs Institute (JBI) Critical Appraisal Tools were employed to assess the methodological quality of the included studies.
Meta-analysis was performed using STATA version 17, applying a random-effects model to account for between-study heterogeneity. The primary outcome was the pooled estimate of the association between cadmium exposure and pancreatic cancer risk, expressed as a summary OR or HR with 95% CIs. Heterogeneity was assessed using the I² statistic, with values above 50% indicating substantial heterogeneity. Publication bias was examined using funnel plots and Egger’s regression test.
Key Findings on Cadmium Exposure and Pancreatic Cancer Risk
The meta-analysis included eleven studies, reflecting data from a total of over 15,000 participants who investigated the relationship between cadmium exposure and pancreatic cancer risk. The pooled analysis revealed a significant association between cadmium exposure and an increased risk of pancreatic cancer, yielding an overall OR of 2.01 (95% CI: 1.30, 2.72). This indicates that individuals exposed to cadmium are more than twice as likely to develop pancreatic cancer compared to those with lower or no exposure (Soleimani et al., 2025).
Notably, substantial heterogeneity was observed across studies, with I² = 98.08%, suggesting that nearly all variation in effect sizes could be attributed to heterogeneity rather than chance. This variability may stem from differences in study designs, populations, and exposure assessment methods. Importantly, both Egger’s and Begg’s tests provided no evidence of publication bias, reinforcing the reliability of the findings.
Subgroup analyses indicated that the association between cadmium exposure and pancreatic cancer risk remained consistent across different geographic regions and study designs. Sensitivity analyses further confirmed the robustness of the pooled estimates, even when excluding studies with a high risk of bias or those contributing significantly to heterogeneity.
Implications for Public Health and Future Research Directions
The findings of this systematic review and meta-analysis underscore cadmium as a potential environmental risk factor for pancreatic cancer. Given the significant association identified, public health initiatives should prioritize efforts to reduce cadmium exposure, particularly in high-risk populations, such as workers in industries with high cadmium exposure. Educational campaigns aimed at increasing awareness of cadmium sources and promoting safer practices are critical for minimizing exposure.
Future research should focus on elucidating the underlying biological mechanisms by which cadmium contributes to pancreatic carcinogenesis. Studies employing advanced exposure assessment techniques and exploring dose-response relationships could enhance our understanding of the cadmium-pancreatic cancer link. Moreover, investigating genetic susceptibility to cadmium toxicity and its interaction with other environmental factors may provide further insights into individual risk profiles.
As the burden of pancreatic cancer continues to rise, identifying and mitigating environmental risk factors such as cadmium exposure is essential for improving prevention and treatment strategies. Ultimately, comprehensive approaches that integrate epidemiological, molecular, and clinical research will be crucial for advancing our knowledge of pancreatic cancer etiology and improving patient outcomes.
Frequently Asked Questions (FAQ)
What is cadmium, and how does it affect health?
Cadmium is a toxic heavy metal commonly found in industrial applications. It can accumulate in the body and is associated with various health issues, including kidney damage and cancer.
How is cadmium exposure linked to pancreatic cancer?
Studies have shown that cadmium exposure increases oxidative stress and inflammation in the pancreas, which may contribute to the development of pancreatic cancer.
What are the main sources of cadmium exposure?
Common sources of cadmium exposure include contaminated food, tobacco smoke, and certain occupational settings, such as battery manufacturing and metal smelting.
What are the key findings of the systematic review on cadmium and pancreatic cancer?
The meta-analysis indicated a significant association between cadmium exposure and pancreatic cancer risk, with individuals exposed to cadmium being more than twice as likely to develop the disease.
What are the public health implications of these findings?
The findings highlight the need for public health initiatives aimed at reducing cadmium exposure and raising awareness about its potential risks, particularly in high-risk occupations.
References
- Soleimani, Y., Nayebi, M., Mahmoudi, S., Daraei, M., Khorsand, S., Jahazi, M. A., Farsi, M. Y., Khalafi, F., Varseh, M., Jarrahi, Z. M. (2025). Cadmium exposure and risk of pancreatic cancer: Systematic review and meta-analysis. PLOS ONE. https://doi.org/10.1371/journal.pone.0319283