The worldwide incidence of melanoma has increased rapidly over the last 50 years.,Melanoma is the most common cancer found in the young adult population, and its incidence is very high among geriatric populations.,The incidence of melanoma varies by sex, and this factor is also associated with differences in the anatomical site melanoma.,Adolescent and young adult women have a higher incidence than men.,This may be, in part, due to the greater use of sunbeds, as well as intentional sun exposure among girls and, in general, risky behaviours in seeking to suntan, due to socially-determined aesthetic needs.,Indeed, the World Health Organization declared that there is sufficient evidence to classify exposure to ultraviolet radiation (sunbed use and sun exposure) as carcinogenic to humans.,Although pigmentation characteristics, such as skin colour, hair and eye colour, freckles and number of common and atypical naevi, do influence susceptibility to melanoma, recommendations regarding prevention should be directed to the entire population and should include avoiding sunbed, covering sun-exposed skin, wearing a hat and sunglasses.,Sunscreen use should not be used to prolong intentional sun exposure.,Primary prevention should be focused mainly on young adult women, while secondary prevention should be focused mainly on elderly men.,In fact, after the age of 40 years, incidence rates reverse, and the incidence of melanoma among men is greater than among women.,This is probably due to the fact that men are less likely than women to examine their own skin or present to a dermatologist for skin examination.
Metastatic melanoma represents a major clinical problem.,Its incidence continues to rise in western countries and there are currently no curative treatments.,While mutation of the P53 tumour suppressor gene is a common feature of many types of cancer, mutational inactivation of P53 in melanoma is uncommon; however, its function often appears abnormal.,In this study whole genome bead arrays were used to examine the transcript expression of P53 target genes in extracts from 82 melanoma metastases and 6 melanoma cell lines, to provide a global assessment of aberrant P53 function.,The expression of these genes was also examined in extracts derived from diploid human melanocytes and fibroblasts.,The results indicated that P53 target transcripts involved in apoptosis were under-expressed in melanoma metastases and melanoma cell lines, while those involved in the cell cycle were over-expressed in melanoma cell lines.,There was little difference in the transcript expression of P53 target genes between cell lines with null/mutant P53 compared to those with wild-type P53, suggesting that altered expression in melanoma was not related to P53 status.,Similarly, down-regulation of P53 by short-hairpin RNA (shRNA) had limited effect on P53 target gene expression in melanoma cells, whereas there were a large number of P53 target genes whose mRNA expression was significantly altered by P53 inhibition in melanocytes.,Analysis of whole genome gene expression profiles indicated that the ability of P53 to regulate genes involved in the cell cycle was significantly reduced in melanoma cells.,Moreover, inhibition of P53 in melanocytes induced changes in gene expression profiles that were characteristic of melanoma cells and resulted in increased proliferation.,Conversely, knockdown of P53 in melanoma cells resulted in decreased proliferation.,These results indicate that P53 target genes involved in apoptosis and cell cycle regulation are aberrantly expressed in melanoma and that this aberrant functional activity of P53 may contribute to the proliferation of melanoma.