Heavy Metal-Contaminated Soils and Gastric Cancer Risk: Molecular Insights and the Relevance of a One Health Perspective

Abstract

Heavy metal contamination in agricultural soils has emerged as a critical environmental and public health issue associated with increased gastric cancer incidence worldwide. Among the most concerning pollutants are cadmium, arsenic, and lead, which persist in the environment and enter the human body primarily through the soil-plant-food chain. This review integrates environmental, molecular, and epidemiological evidence to explain how these metals alter gastric mucosal biology and promote carcinogenesis. Mechanistically, cadmium, arsenic, and lead trigger oxidative stress, mitochondrial dysfunction, DNA damage, and epigenetic reprogramming, resulting in genomic instability, resistance to programmed cell death, and the transformation of epithelial cells into invasive phenotypes. These molecular disruptions interact with Helicobacter pylori infection, microbial imbalance, chronic inflammation, and hypoxia-driven remodeling of the gastric stroma, all of which enhance angiogenesis and tumor progression. Advanced experimental platforms, such as gastric organoids, immune co-cultures, and humanized animal models, are improving the understanding of these complex interactions. Adopting a One Health perspective reveals the continuity between environmental contamination, agricultural production, and human disease, underscoring the importance of integrative monitoring systems that combine soil and crop analysis with molecular biomarkers in exposed populations. Strengthening this interdisciplinary approach is essential to design preventive strategies, guide remediation policies, and protect human, animals, and environmental health.

Keywords: One Health; arsenic; cadmium; environmental contamination; gastric cancer; heavy metals; lead.

Figure 1

Influence of Soil pH and Redox Potential on Cadmium, Arsenic, and Lead Speciation, Mobility, and Plant Bioavailability. Acidic soils (low pH) increase Cd mobility and bioavailability, whereas alkaline conditions (high pH) enhance As mobility through arsenate [As(V)] reduction to arsenite [As(III)] under reducing conditions. Lead (Pb²⁺) remains largely immobile, though its mobility slightly increases in acidic or oxidizing environments. Overall, the bioavailability of these metals to plants is strongly governed by pH and Eh, with acidic soils posing the greatest risk for Cd uptake and anoxic conditions increasing the toxicity of As.

Figure 2

Molecular mechanisms underlying heavy metal-induced tumorigenesis. A crucial factor in their carcinogenic potential is the ability to drive persistent inflammation, which acts as a bridge between exposure and tumor formation. Chronic inflammation enhances DNA damage, fuels cell proliferation, weakens repair systems, and promotes epithelial–mesenchymal transition (EMT), enabling greater invasiveness and metastatic potential. This state is further reinforced by cytokines such as IL−1, IL−6, IL−18, TNF-α, and TGF-β, with IL−1 shifting from its usual protective function to one that facilitates cancer progression under sustained inflammatory conditions [72].