The improved understanding of the molecular events leading to different tumor entities by de-differentiation of the same cell type has begun to pave the way for modulating new molecular targets therapeutically with small molecules.To shed further light on the ongoing debate whether sunbed use may increase melanoma risk, we have critically assessed the scientific literature that is at present available, focussing on a meta-analysis that we published recently. Our literature search identified several meta-analyses that report a weak association for ever-exposure to UV radiation from a solarium with melanoma risk. However, the quality of studies included in these meta-analyses and the resulting evidence levels and grades of recommendation were very low due to the lack of interventional trials and because of severe limitations of many of the observational studies. The results of cohort and case-control studies published until today do not prove causality, not even by the Hill criteria.  https://www.selleckchem.com/products/hc-258.html  The overall quality of these observational studies and the resulting evidence levels are low due to severe limitations (including unobserved or unrecorded confounding), which leads to bias. It must be recognized that in the majority of studies, published to date, many of the confounding factors, including sun exposure, sunburns and skin type, have not been adequately and systematically recorded and adjusted for. We conclude that the many limitations of the individual studies and the resulting low levels of evidence and grades of recommendation do at present not allow postulation of a causal relationship between solarium use and melanoma risk. At present, there is no convincing evidence that moderate/responsible solarium use increases melanoma risk.Solar UV exposure is critical and complex in the etiology and prognosis of skin cancer, particularly cutaneous malignant melanoma. Sun exposure and one of its "derivatives," vitamin D, have been implicated in protection against mortality from melanoma. However, the relationships are inconsistent. At this time, it is not possible to make clear recommendations for or against sun exposure in relationship to melanoma prognosis. However, this relationship deserves continued exploration.Melanoma and keratinocyte skin cancer (KSC) are the most common types of cancer in White-skinned populations. Both tumor entities showed increasing incidence rates worldwide but stable or decreasing mortality rates. Rising incidence rates of cutaneous melanoma (CM) and KSC are largely attributed to increasing exposure to ultraviolet (UV) radiation, the main causal risk factor for skin cancer.Incidence rates of KSC, comprising of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are much higher than that of melanoma. BCC development is mainly the cause of an intensive UV exposure in childhood and adolescence, while SCC development is related to chronic, cumulative UV exposure over decades. Although mortality is relatively low, KSC is an increasing problem for health care services causing significant morbidity.Cutaneous melanoma is rapidly increasing in White populations, with an estimated annual increase of around 3-7% over the past decades. In contrast to SCC, melanoma risk is associated with intermittent and chronic exposure to sunlight. The frequency of its occurrence is closely associated with the constitutive color of the skin and the geographical zone. Changes in outdoor activities and exposure to sunlight during the past 70 years are an important factor for the increasing incidence of melanoma. Mortality rates of melanoma show stabilization in the USA, Australia, and in European countries. In the USA even dropping numbers of death cases were recently reported, probably reflecting efficacy of the new systemic treatments.Among younger cohorts in some populations (e.g., Australia and New Zealand,), stabilizing or declining incidence rates of CM are observed, potentially caused by primary prevention campaigns aimed at reducing UV exposure. In contrast, incidence rates of CM are still rising in most European countries and in the USA. Ongoing trends towards thinner melanoma are largely ascribed to earlier detection.Increasing sun exposure is related to lower prevalence of death in cardiovascular disease (CVD), type 2 diabetes, and other noncancer non-CVD. In this chapter we aim to make a short update on the knowledge regarding sun exposure and all-cause mortality. Data support the hypothesis that low sun exposure habits are a major risk factor for all-cause mortality. Low sun exposure is related to an increased risk of death due to CVD and noncancer/non-CVD, and a minor reduction in risk of cancer. Active sun exposure habits have a dual effect; it increases the incidence of skin cancer, but also improves the prognosis in terms of all-cause mortality. In a low solar intensity region, we should carefully assess both risk and benefits of sun exposure in order to obtain balanced recommendations.Increasing scientific evidence supports the link between vitamin D and cancer risk. The active metabolite 1,25(OH)2D exerts its activity by binding to the vitamin D receptor (VDR), an intracellular receptor that mediates transcriptional activation and repression of target genes. The binding of 1,25(OH)2D to VDR is able to regulate hundreds of different genes. VDR is active in virtually all tissues including the colon, breast, lung, ovary, bone, kidney, parathyroid gland, pancreatic b-cells, monocytes, T lymphocytes, melanocytes, keratinocytes, and also cancer cells.The relevance of VDR gene restriction fragment length polymorphisms for various types of cancer has been investigated by a great number of studies.We have carried out a systematic review of the literature to analyze the relevance of more VDR polymorphisms (Fok1, Bsm1, Taq1, Apa1, and Cdx2) for individual malignancies considering ethnicity as a key factor for heterogeneity.Up to December 2018, we identified 176 independent studies with data to assessk of some cancer sites and in future studies VDR genetic variation should be integrated also with assessment of vitamin D status and stratified by ethnicity.