Paving the Way to Elucidate Hg's Role in Tumorigenesis.

Tumorigenesis can be induced by diverse environmental carcinogens, with mercury (Hg)-a global pollutant that accumulates in humans throughout life, crosses the blood-brain and placental barriers, and is poorly excreted-classified as a Group 2B carcinogen; however, its contribution to human tumorigenesis remains insufficiently characterized. This critical knowledge gap stems primarily from confounding effects of human co-exposure to other carcinogens and detoxifying agents, coupled with unclear correlations along the external exposure-internal Hg burden-tumorigenesis continuum due to insufficient organ-specific Hg data in humans. To improve the understanding of Hg's role in tumorigenesis, we propose a research paradigm that integrates: 1) advancing Hg speciation analysis in human tissues and internal dynamics of Hg through in vivo transformation studies, to map organ-specific Hg distributions; and 2) constructing a comprehensive database of demographic factors, Hg exposure profiles, and tumor biomarkers for artificial intelligence-driven analyses to disentangle Hg-specific effects from confounding factors. Bridging the gap between Hg exposure and tumorigenesis could help identify overlooked tumorigenic factors, advance targeted prevention strategies, and guide decision-making in environmental and public health, ultimately improving public health outcomes.