This document summarizes epidemiological data and risk factors related to melanoma. It discusses that melanoma incidence has increased significantly in fair-skinned populations over the last century. Genetic factors like mutations in the CDKN2A and CDK4 genes confer high penetrance for melanoma risk, while variants in the MC1R gene are a low penetrance risk factor. Environmental exposures like ultraviolet radiation from the sun are important exogenous risk factors for developing melanoma.

1. The International School of Vitiligo & Pigmentary Disorders Barcelona, 2-5 November 2011 Edizioni Fernando Folini, Alessandria 2008 Torello Lotti Department of Dermatologic Sciences University of Florence, Italy Melanoma epidemiology, etiopathogenesis and prevention

2. Melanoma EPIDEMIOLOGY

8. Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, Boyle P, editors. Cancer incidence in five continents. Vol. IX. Lyon: IARC (IARC Scientific Publications No. 160); 2007. http://www-dep.iarc.fr/CI5_IX_frame.htm Cutaneous melanoma incidence for selected populations of Australia, the US and Europe for the years 1998–2002. Rates standardized according to the world standard population. Data retrieved from the cancer incidence in five continents vol. IX database

9. Cutaneous melanoma incidence rates/100.000 person/year (standardized on global population) for sex and geographical areas. Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002 Cancer Incidence, mortality and prevalence woeldwide IARC cancer base No.5, version 2.0. IARC press, Lyon, 2004. Geographical areas Incidence rates Men Women Australia/New Zeland 29.4 37.7 North America 11.7 11.4 Western Europe 10.3 7.3 Southern Europe 5.5 6.0 South Africa 4.1 5.4 Eastern Europe 3.8 3.3 Melanesia 2.9 4.8 East Africa 2.3 1.2 South America 2.3 2.4 Central Africa 2.2 2.2 Central America 1.7 1.3 Western Asia 1.5 1.6 Caraibi 1.1 1.0 Western Africa 0.9 1.1 Micronesia o.7 1.2 North Africa 0.5 0.7 South-East Asia 0.5 0.5 South-Center Asia 0.4 0.4 Eastern Asia 0.2 0.3 Polinesia 0.0 5.1

10. Melanoma ETIOPATHOGENESIS Risk factors Melanoma genesis

14. Mancini C, Fargnoli MC, Suppa M, et al. Aspetti genetico-molecolari. In: De Giorgi V, Aricò M, Lotti T, eds. Il melanoma.Prevenzione, diagnosi e terapia. Tortona: Fernando Folini; 2008. pp 11-14. melanoma affected woman melanoma affected man = dead Genealogical tree of melanoma-affected family

37. Melanoma genesis

38. Nearly 30% of cases derives from melanocytic nevi (ie, common, congenital, and atypical/dysplastic types) The sequence of events in which normal melanocytes transform into melanoma cells, referred to as melanomagenesis , is still poorly understood. Melanomagenesis about 70% of cases arise de novo (ie, not from a preexisting pigmented lesion). Palmieri G, Capone M, Capone M, Main roads to melanoma Journal of Translational Medicine 2009;7:art86 . Primary cutaneous melanoma

42. Both types of lesions induced by UVB rays, i.e., 6–4 photoproducts (6-4-PP) and pyrimidine dimers (PD) , can lead to genetic mutations such as the C T or CC T T transitions (the latter mutation being the hallmark of UV-induced mutagenesis). Molecular and carcinogenic responses of melanocytes to UV radiation Jhappan C, Noonan FP, Merlino G. Ultraviolet radiation and cutaneous malignant melanoma. Oncogene 2003; 2 2.

44. Transmission electron micrograph (TEM) of a melanocyte from human malignant melanoma. From: http://www.sciencephoto.com/media/253749/enlarge An overproduction of melanin is indicated by the small black areas around the periphery of the cell. The cell nucleus has the appearance of a fried egg, with a central dark nucleolus .

45. Transmission electron micrograph (TEM) of melanosomes within a malignant melanocyte . From: http://www.sciencephoto.com/media/253750/enlarge

46. Melanoma PREVENTION Primary prevention photoprotection Secondary prevention early diagnosis

47. Photoprotection Behavioral norms Sunscreen use Melanocortin analog administration

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