Arsenic exposure and skin cancer: Mechanisms, clinical evidence and public health implications (Review)

Skin is among the most frequent sites of cancer diagnosis, and the global incidence of skin cancer continues to rise despite extensive public health initiatives and preventive strategies. Arsenic, a ubiquitous environmental metalloid classified as a Group 1 carcinogen, remains an important concern due to widespread exposure through contaminated drinking water, food sources and occupational contact. Arsenic‑associated skin carcinogenesis involves complex, interdependent molecular processes and has been linked to the disruption of redox signalling, altered DNA damage signalling and repair responses as well as epigenetic reprogramming. In keratinocytes, arsenic perturbs redox and stress‑response pathways and may disrupt genome maintenance and cellular stress signalling in experimental systems. Arsenic may also alter microRNA networks and affect telomere and mitochondrial homeostasis, although the contribution of these processes to malignant transformation remains context‑dependent; in melanoma, the carcinogenic mechanisms of arsenic are less well characterized. Clinically, arsenic is recognized as a carcinogen in non‑melanoma skin cancer (NMSC) and evidence from high‑exposure endemic regions, together with occupational cohorts, suggest a dose‑responsive association. For melanoma, clinical evidence is more heterogeneous and subject to substantial potential confounding, although some studies suggest modest risk elevation in high‑exposure or occupational settings. Collectively, convergent mechanistic, experimental and epidemiological data support arsenic as an independent carcinogen, particularly in NMSC. These findings underscore the need for heightened clinical vigilance, particularly in exposed populations, and call for renewed public health strategies and regulatory frameworks to mitigate the persistent global burden of arsenic‑associated skin cancer.