The Influence of Pigment Transfer on the Risk of Developing Melanoma: The Significance of the Melanocyte ‘Amputation Cycle’

It has been shown that cancer incidence is not only a function of the size of the population at risk but is strongly associated with the turnover rate of the tissue concerned. There is a strong negative correlation between melanoma incidence and the degree of skin pigmentation, and yet the melanocyte density is the same for all races. The proposal advanced in this communication is that the probability of undergoing malignant change is critically dependent on the melanocyte turnover and that this is regulated by the pigmentation process. In melanocytes, the division rate is influenced by the process of pigment donation, probably by a mechanism whereby the continual cytoplasmic loss due to cytocrine transfer of melanosomes (termed the ‘Amputation Cycle’) inhibits replication. Consequently the turnover of melanocyte stem cells in heavily pigmented epidermis will be diminished, and this is held to account for the strong negative correlation between the degree of skin pigmentation and melanoma incidence.