Skin cancer – Primary and secondary prevention (information campaigns and screening) – With a focus on children & sunbeds

Abstract

Solar and artificial (sunbed) UV-exposure is the main risk factor for the development of epithelial skin cancer (basal cell carcinoma, BCC, and squamous cell carcinoma, SCC) as well for malignant melanoma (MM). UV exposure in childhood and adolescence is especially important. Therefore, adequate methods of primary prevention have continuously to be used and to be developed further to target these age-groups in order to reduce the risks of intensive UV-exposure. Primary prevention can effectively be combined with secondary prevention (early detection, screening) to reduce the burden of skin cancer and to decrease incidence, morbidity and mortality.

Introduction

Solar ultraviolet (UV-) radiation as well as artificial UV (e.g., from sunbeds) is known to represent the most prominent risk factor for the induction of skin cancer (Armstrong and Kricker, 2001, Cleaver and Crowley, 2002, Greinert, 2009, Leiter and Garbe, 2008, Norval et al., 2007, Ramos et al., 2004). Due to the ubiquitous nature of solar UV, recreational and occupational behavior of the public and increasing use of artificial UV in sunbeds (especially by adolescents) skin cancer incidence is steadily increasing, making skin cancer (squamous cell carcinoma, SCC, basal cell carcinoma, BCC, and malignant melanoma, MM) the most frequent cancer in the white population worldwide (Greinert, 2009).

UV-radiation (UVB = 280–315 nm and UVA = 315–400 nm) induces signature mutations in the genome of human skin cells (Ikehata and Ono, 2011). These are C–T transitions and CC–TT tandem mutations which are characteristic for a misrepair of UV-induced pre-mutagenic DNA lesions (Cadet et al., 2005, Douki et al., 2003, Mouret et al., 2008, Rochette et al., 2003). Interestingly, the recent first whole genomic sequencing of a human melanoma metastasis reveals that a huge majority of detected mutations are of UV-signature type, clearly proving the role of UV radiation in melanoma genesis (Pleasance et al., 2010).

The main pre-mutagenic DNA-lesion leading to UV-signature mutations is the cyclobutane-pyrimidine dimer (CPD), which has been shown to be produced by UVB radiation in human skin cells as the most prominent DNA-lesion (Mouret et al., 2008). However, recent results show that also UVA is able to induce CPDs. Although the photochemical mechanisms have still to be elucidated, it turned out that UVA-induced CPDs comprise the main pre-mutagenic lesion in human skin cells (Mouret et al., 2006, Mouret et al., 2010). These results clearly underline an important role of UVA (which comprise 95% of solar UV) in basic mechanisms involved in skin carcinogenesis. The question, however, which part of the UV-spectrum (UVB, UVA), and which molecular events, pathways and specific genes are involved in photocarcinogenesis has further to be studied in more detail. Furthermore, the role of epidermal stem cells, their epigenetic regulation and the role of UV-induced epigenetic alterations in these target cells has to be investigated in the future to understand the prominent contributions of these factors for skin cancer development (Greinert, 2009).

The International Agency for the Research on Cancer (IARC) has grouped solar UV (UVB = 280–315 nm and UVA = 315–400 nm) as well as UV-radiation used in sunbeds in Group 1 (“carcinogenic to humans”) (El Ghissassi et al., 2009). This has been reasoned by the overwhelming evidence coming from epidemiological data and in-vitro and in-vivo experiments which prove a causal connection between UV and skin cancer (see above). Because the main risk factor for induction and development of skin cancer (-natural and artificial UV-) is known so well, and early forms of skin cancer (also malignant melanoma) can be treated very successfully, skin cancer can be prevented by means of primary and secondary prevention. However these forms of prevention have to be performed continuously and well organized to achieve the final goal of reducing skin cancer incidence, morbidity and mortality. Special efforts have to be undertaken to target children because UV-exposure in childhood and adolescence is known to be an important risk factor for developing skin cancer. One of the reasons for that may be the fact that skin cancer most probably develops from (epidermal) stem cells in human skin, which differ in their localization between children’s and adult’s skin (see Volkmer et al. this journal issue).