Abstract
<jats:p>Across the globe, cancer incidence continues its upward course, with environmental exposures playing a decisive role alongside genetic predisposition. Heavy metals have emerged as persistent environmental carcinogens due to their propensity for bioaccumulation and long-term systemic toxicity. It is increasingly recognized that chronic exposure to low doses can exert significant biological effects through cumulative mechanisms and nonlinear dose–response relationships, particularly within the endocrine system. Current epidemiological and experimental evidence indicates a strong mechanistic link between chronic metal exposure and endocrinerelated carcinogenesis. The promotion of hormone-dependent tumours by heavy metals is facilitated by multiple interconnected pathways, including disruption of cellular redox homoeostasis, the accumulation of DNA lesions, loss of genomic integrity, and epigenomic remodelling. Furthermore, their interactions with the tumour microenvironment (TME) contribute to the dynamic reconfiguration of cancer-related signalling pathways. Mendelian randomization analyses provide further evidence supporting potential causal relationships between metal exposure and various malignancies, including those of the thyroid, breast, and reproductive organs. These findings emphasize the dose-dependent and context-specific nature of metal-induced malignancy, thus providing significant implications for optimizing clinical risk frameworks and developing targeted prevention strategies. In determining the level of exposure to endocrine-disrupting chemicals, it is crucial to develop clinically diagnostic approaches, identify new, reliable, cost-effective, and easily applicable biomarkers (even those that can be implemented through machine learning), and clarify these underlying mechanisms in more detail to develop individual protective and preventive interventions.</jats:p>