Iron overload and its association with cancer risk in humans: evidence for iron as a carcinogenic metal.

Unlike arsenic, chromium, or nickel, the carcinogenicity of iron is still under debate. In this review, evidence for iron as a carcinogenic metal was summarized from epidemiological, animal, and cell culture studies. The role of iron in various cancers, such as colorectal cancer and liver cancer was presented. Recent advancements on the molecular mechanisms of iron carcinogenesis were also reviewed. These include: (1) iron autoxidation involving only Fe(2+)+O2 in oxidant formation in biological systems and its pH dependency; (2) activation of oxidative responsive transcription factors and pro-inflammatory cytokines; and (3) iron-induced hypoxia signaling.