Metal carcinogens and cancer: integrating genetic and epigenetic perspectives

People around the globe are affected by extensive environmental and occupational exposure to heavy metals, which poses a significant threat to various health hazards, with cancer being a major concern. These toxic metals are ubiquitously found in food, air, water, and industrial, agricultural, or pharmaceutical applications. Being non-biodegradable, they accumulate in the living organism. The prolong exposure to these metals can result into hazardous effects in the many organs including respiratory problems, gastrointestinal disorders, renal issues, and skin lesions etc. Arsenic (As), Cadmium (Cd), Chromium (Cr), Nickel (Ni), Mercury (Hg), and Lead (Pb) are the most common heavy metals causing carcinogenicity through both genetic and epigenetic mechanisms. The literature indicates that DNA damage, deregulation of gene expression, interference with cell signaling, etc., contribute to metal-induced carcinogenesis. Changes in epigenetic processes, such as DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs, can disturb normal cell function and may even lead to cancer. However, the molecular mechanism remains poorly understood. Advancements in the field have underscored the critical roles of genetic mutations and epigenetic modifications in metal-induced tumor formation. This review gives a comprehensive overview of the function of metals in causing cancer, focusing on pathways such as genotoxicity, mutagenesis, epigenetic modification, and cancer-related signaling. Furthermore, with the ultimate goal of reducing the burden of this disease, the targeted preventive strategies, such as reducing the emission of these toxic metals into the environment from mining to industries, or other sources, and the need for social interventions, have been discussed.