P06-12 Heavy metals and skin cancer: From pathophysiology to public health

Cutaneous malignancies, including melanoma and nonmelanoma skin cancers (NMSCs), are among the most prevalent cancers globally. While ultraviolet (UV) radiation remains the principal environmental etiologic factor, a growing body of evidence implicates chronic and high-level exposure to specific heavy metals as co-contributors to cutaneous carcinogenesis. This review aims to critically evaluate the epidemiological, mechanistic, and toxicological literature linking key heavy metals to skin cancer. We conducted a comprehensive search of the literature using a combination of controlled vocabulary and free-text keywords pertaining to specific heavy metals. The PubMed, Scopus, Cochrane Library and Google Scholar databases were searched up to February 2025. Several heavy metals are implicated in the pathogenesis of cutaneous malignancies. Mechanistically, these metals converge on multiple pathways. They exert direct genotoxic effects and disrupt DNA repair enzymes, induce sustained oxidative stress, and create significant epigenetic alterations, including hypermethylation of tumor suppressor genes. In tandem, they compromise immune surveillance and often synergize with UV irradiation, amplifying the likelihood of malignant transformation. Arsenic is consistently associated with NMSCs, and there is strong evidence linking arsenic to melanoma, but the association is less definitive. For cadmium the epidemiological findings are mixed; some studies indicate no clear linear associations with NMSCs, though there is evidence for dose-dependent and nonlinear relationships. Chromium, especially in its hexavalent form (Cr[VI]), enhances UV-induced skin carcinogenesis in experimental models, primarily through reactive oxygen species. However, human epidemiological data are sparse and provide inconsistent results. Lead demonstrates genotoxicity in vitro , but epidemiological data fail to support a definitive association with melanoma or NMSC at typical exposure levels. The limited evidence suggests that mercury exposure, particularly in the form of methylmercury, is associated with NMSCs and melanoma; its carcinogenic effects appear to be magnified in individuals who consume alcohol. Epidemiological evidence directly linking nickel exposure to skin cancer in human populations remains limited and equivocal. Recognition of heavy metal exposure as a modifiable cofactor in cutaneous malignancy has significant implications for public health policy, particularly in vulnerable populations with cumulative environmental and occupational risks. Future research should prioritize longitudinal exposure assessment, the elucidation of gene-environment interactions, and the development of targeted screening strategies to mitigate skin cancer risk attributable to heavy metals.