Some genotypic and environmental conditions of the host in cutaneous malignant melanoma.

The factors involving the development of melanoma vary according to the phenotype and environment conditions experienced by the host MC1R variant alleles that are associated with increased melanoma risk are likely to sensitize melanocytes to DNA damage by ultraviolet (UV) exposure, and the interactions between UV radiation and the genome induce melanoma. In fact, the non-functional MC1R cells have a very slow rate of cyclobutane pyrimidine dimers removal. The most significant mutations induced by UV in the skin occur in the CDKN2A gene being the major target of UV, that encodes 2 distinct proteins cell cycle regulators: p16INK4A and p14ARF. Inactivation of both tumor suppressors results in escape from cell cycle arrest because of disruption of the G1/S restriction point The outcome is premature cell cycle progression and incomplete repair of DNA damage that leads to genomic instability and mutations. In fact, the signaling pathways of UV in melanocytes reveal the complex interrelationship between the pathways that regulate survival, proliferation and melanogenesis