Thinking about the role (largely ignored) of heavy metals in cancer prevention: hexavalent chromium and melanoma as a case in point.

Ultraviolet (UV) light exposure accounts for only 40-50% of the attributable risk for cutaneous melanoma (CM); also classical UV-induced lesions are rare in melanomas (especially among CM with NRAS or BRAF mutations). It is therefore likely that an additional environmental factor exists as familial and genetic factors play a role in less than 5%. A large amount of (largely forgotten) epidemiologic data indicates that heavy metal exposure is strongly associated with the development of CM. Also, epidemiologic studies of patients with joint replacement indicate a marked subsequent time-related increase in melanoma in patients with metal-on-metal hip arthroplasties. In these patients chromium and cobalt levels rise to 10x normal and stay elevated at levels two- to threefold normal for at least 10 years. Chromium is widely used in industry for its anticorrosive and steel-strengthening properties and is widespread in everyday materials. Our hypothesis is therefore that chromium, alone or in conjunction with UV, plays a major role in the pathogenesis of CM. We have incubated human neonatal melanocytes for more than 10 weeks in the presence of a wide range and concentrations of metals without effect except by hexavalent chromium Cr(VI)and to a lesser degree Co²(+). After prolonged culture, chromium-incubated cells produced foci and when replated secondary colonies formed. We have just begun to study this phenomenon in more detail and studies without and with different wavelengths of UV will be explored. Of interest is that aneuploidy (a universal chromosomal change in cutaneous melanoma) in lymphocytes in patients with hip-on-hip metal prostheses has been demonstrated by others.