Vitamin D in cutaneous carcinogenesis Part II

Department of Dermatology, Stanford University, Stanford, California. Electronic address: .
Journal of the American Academy of Dermatology (Impact Factor: 4.45). 11/2012; 67(5):803.e1-803.e12. DOI: 10.1016/j.jaad.2012.05.044
Source: PubMed


Skin cancer is the most common cancer in the United States. Exposure to ultraviolet radiation is a known risk factor for skin cancer but is also the principal means by which the body obtains vitamin D. Several studies have suggested that vitamin D plays a protective role in a variety of internal malignancies. With regard to skin cancer, epidemiologic and laboratory studies suggest that vitamin D and its metabolites may have a similar protective effect. These noncalcemic actions of vitamin D have called into question whether the current recommended intake of vitamin D is too low for optimal health and cancer prevention. Part I will review the role of vitamin D in the epidermis; part II will review the role of vitamin D in keratinocyte-derived tumors to help frame the discussion on the possible role of vitamin D in the prevention of skin cancer.

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    • "These effects are most likely mediated by the activation of VDR-and peroxisome proliferator-activated receptor-signalling pathways [19]. In vivo, the study of the effect of vitamin D on the risk of skin cancer is more difficult, given that (a) exposure to UV radiation is considered as the main risk factor for the development of both cutaneous melanoma (CM) [20] [21] and non-melanoma skin cancer (NMSC) [22], and (b) the dietary intake of pre-vitamin D, either through food or vitamin supplements, has an uncertain association, if any, with its activity in the skin [1]. Evidence for the role of vitamin D in the pathogenesis of skin cancer is provided by findings on vitamin D receptor as well [23] [24]. "
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    ABSTRACT: Vitamin D is formed mainly in the skin upon exposure to sunlight and can as well be taken orally with food or through supplements. While sun exposure is a known risk factor for skin cancer development, vitamin D exerts anti-proliferative and pro-apoptotic effects on melanocytes and keratinocytes in vitro. To clarify the role of vitamin D in skin carcinogenesis, we performed a review of the literature and meta-analysis to evaluate the association of vitamin D serum levels and dietary intake with cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) risk and melanoma prognostic factors. Twenty papers were included for an overall 1420 CM and 2317 NMSC. The summary relative risks (SRRs) from random effects models for the association of highest versus lowest vitamin D serum levels was 1.46 (95% confidence interval (CI) 0.60-3.53) and 1.64 (95% CI 1.02-2.65) for CM and NMSC, respectively. The SRR for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63-1.13) for CM and 1.03 (95% CI 0.95-1.13) for NMSC. Data were suggestive of an inverse association between vitamin D blood levels and CM thickness at diagnosis. Further research is needed to investigate the effect of vitamin D on skin cancer risk in populations with different exposure to sunlight and dietary habits, and to evaluate whether vitamin D supplementation is effective in improving CM survival.
    Full-text · Article · Jul 2014 · European journal of cancer (Oxford, England: 1990)
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    • "Like most other skin cells, keratinocytes express VDR (Lehmann et al., 2004; Holick, 2007); in these cells, 1,25-dihydroxyvitamin D, blocks proliferation and promotes differentiation in vitro (Lehmann et al., 2004; Holick, 2007; Haussler et al., 2012). Interestingly, it has been reported that the combination of 1,25-dihydroxyvitamin D and the retinoic acid metabolite isotretinoin is efficient in the therapy of precancerous skin lesions and of non-melanoma skin cancer (cutaneous squamous and basal cell carcinomas) (Tang et al., 2012a,b; Mason and Reichrath, 2013). Moreover, it has been demonstrated that VDR ablation promotes chemically induced skin carcinogenesis (Tang et al., 2012a,b; Mason and Reichrath, 2013). "
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    ABSTRACT: P53 and its family members have been implicated in the direct regulation of the vitamin D receptor (VDR). Vitamin D- and p53-signaling pathways have a significant impact on spontaneous or carcinogen-induced malignant transformation of cells, with VDR and p53 representing important tumour suppressors. VDR and the p53/p63/p73 proteins all function typically as receptors or sensors that turn into transcriptional regulators upon stimulus, with the main difference being that the nuclear VDR is activated as a transcription factor after binding its naturally occurring ligand 1,25-dihydroxyvitamin D with high affinity while the p53 family of transcription factors, mostly in the nucleoplasm, responds to a large number of alterations in cell homeostasis commonly referred to as stress. An increasing body of evidence now convincingly demonstrates a cross-talk between vitamin D- and p53-signaling that occurs at different levels, has genome-wide implications and that should be of high importance for many malignancies, including non-melanoma skin cancer. One interaction involves the ability of p53 to increase skin pigmentation via POMC derivatives including alpha-MSH and ACTH. Pigmentation protects the skin against UV-induced DNA damage and skin carcinogenesis, yet on the other hand reduces cutaneous synthesis of vitamin D. A second level of interaction may be through the ability of 1,25-dihydroxyvitamin D to increase the survival of skin cells after UV irradiation. UV irradiation-surviving cells show significant reductions in thymine dimers in the presence of 1,25-dihydroxyvitamin D that are associated with increased nuclear p53 protein expression, and significantly reduced NO products. A third level of interaction is documented by the ability of vitamin D compounds to regulate the expression of the murine double minute 2 (MDM2) gene in dependence of the presence of wild-type p53. MDM2 has a well established role as a key negative regulator of p53 activity. Finally, p53 and famil
    Full-text · Article · Jun 2014 · Frontiers in Physiology
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    • "k people , who cannot photosynthesize vitamin D under their pigmented skins , are more prone to develop prostate cancers . Research studies reported that Vitamin D plays a protective task in a variety of internal malignancies whereas epidemiologic and laboratory studies suggest that Vitamin D may have a comparable shielding effect on skin cancer ( Tang et al . , 2012 ) . Epidemiology studies argued that the levels of sunlight and cancer are inversely proportional . While coming to breast cancer , Stearns and Visvanathan ( 2013 ) reported that vitamin D reduces the risk of breast cancer development . Vitamin D receptor ( VDR ) gene polymorphisms have been reported to influence the susceptibility to b"
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    ABSTRACT: Vitamin D supplementation appears to be potential for reducing risks of cancer, cardiovascular disease, and other chronic diseases, existing evidence on its benefits and risks is inadequate and debatable. Questions remain as to whether supplementation of Vitamin D playing any role in the above mentioned diseases. In the absence of compelling evidence for benefit, taking supplement is producing any risk or not. While sorting the various positive and negative claims for Vitamin D, it attracts an urgent need for further research and review on reports to answer fundamental questions about the risks and benefits of supplementation. There still remains a great need to advance our understanding regarding the effectiveness of Vitamin D. This review gives an overview on disputes of Vitamin D supplementation that is convincing and interventional regarding burning issues of Vitamin D therapy. Beyond its use to prevent osteomalacia or rickets, the evidence for other health effects of vitamin D supplementation in the general inhabitants is conflicting. It is a well known predictability that any effective substance also has unwanted side effects, so clear cut evidence regarding the safety is required before supplementing Vitamin D for pathological conditions and other health benefits.
    Full-text · Article · Jan 2014 · International Food Research Journal
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