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

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.