Sun Exposure and Melanoma, Certainties and Weaknesses of the Present Knowledge

Abstract

Sun exposure is the main risk factor for cutaneous malignant melanoma (CMM). However, the UV-related pathogenetic mechanisms leading to CMM are far to be fully elucidated. In this paper we will focus on what we still don't fully know about the relationship between UVR and CMM. In particular, we will discuss: the action spectrum of human CMM, how different modalities of exposure (continuous/ intermittent; erythemal/ suberythemal) relate to different CMM variants, the preferential UVR induced DNA mutations observed in different CMM variants, the role of UV-related and UV-unrelated genetic damages in the same melanoma cells. Moreover, we will debate the importance of UVA induced oxidative and anaerobic damages to DNA and other cell structures and the role of melanins, of modulation of innate and acquired immunity, of vitamin D and of chronic exposure to phototoxic drugs and other xenobiotics. A better understanding of these issues will help developing more effective preventative strategies and new therapeutic approaches.

Keywords: UVA; UVB; melanoma; sun exposure; vitamin D.

Figure 1

UV- induced DNA damages and their waveband dependency.

Figure 2

Selected inflammatory molecular pathways that are triggered by UVR in melanocytes.

Figure 3

Associations of the clinical variants of CMM with modalities of exposures and driver mutations. Legend: SSM, superficial spreading melanoma; LMM, Lentigo Maligna Melanoma; ALM, acral lentiginous melanoma; MuM, mucosal melanoma; UvM, uveal melanoma (references in the text).

Figure 4

Interplay of UV related, UV unrelated, genetic and stochastic factors in the pathogenesis of cutaneous Malignant Melanoma (CMM).