Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have carried out melanoma case-control comparisons for six vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) and serum 25-hydroxyvitamin D(3) levels in order to investigate the role of vitamin D in melanoma susceptibility. There was no significant evidence of an association between any VDR SNP and risk in 1028 population-ascertained cases and 402 controls from Leeds, UK. In a second Leeds case-control study (299 cases and 560 controls) the FokI T allele was associated with increased melanoma risk (odds ratio (OR) 1.42, 95% confidence interval (CI) 1.06-1.91, p=0.02). In a meta-analysis in conjunction with published data from other smaller data sets (total 3769 cases and 3636 controls), the FokI T allele was associated with increased melanoma risk (OR 1.19, 95% CI 1.05-1.35), and the BsmI A allele was associated with a reduced risk (OR 0.81, 95% CI 0.72-0.92), in each instance under a parsimonious dominant model. In the first Leeds case-control comparison cases were more likely to have a higher body mass index (BMI) than controls (p=0.007 for linear trend). There was no evidence of a case-control difference in serum 25-hydroxyvitamin D(3) levels. In 1043 incident cases from the first Leeds case-control study, a single estimation of serum 25-hydroxyvitamin D(3) level taken at recruitment was inversely correlated with Breslow thickness (p=0.03 for linear trend). These data provide evidence to support the view that vitamin D and VDR may have a small but potentially important role in melanoma susceptibility, and putatively a greater role in disease progression.
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PMID:Vitamin D receptor gene polymorphisms, serum 25-hydroxyvitamin D levels, and melanoma: UK case-control comparisons and a meta-analysis of published VDR data. 1961 88

Solar radiation is both the main cause of all types of skin cancer, including cutaneous malignant melanoma (CMM), and the main source of vitamin D accompanied by its beneficial effects. The dilemma lies in that increased sun exposure could lead to an increase in skin cancers and yet is necessary for the better prognosis of internal cancers. Solar radiation varies in intensity and spectral composition with geographic location and time. Of central interest in the present context is that the UVA/UVB ratio can vary. Thus, the UVA/UVB ratio increases with decreasing solar elevation. The ratio is also larger for most sun beds than that in the midday sun, but similar to that in the afternoon sun. This may have large health implications, since vitamin D is exclusively generated by UVB, while UVA and UVB likely play a role in the onset of CMM. Sun and sun beds act similarly: one quantum of radiation at a given wavelength has the same biological effect, irrespective of the source from which it comes. The winter levels of vitamin D are 10 to 100% lower than the summer levels in most populations, but can be brought up to summer levels by moderate sun bed exposure. Doses of 200 IU of vitamin D per day are not sufficiently large to maintain a summer vitamin D status in winter. At high latitudes (>40 degrees) the sun provides no vitamin D in winter. A number of epidemiological studies, interventional studies, animal studies and cell experiments show that vitamin D reduces the risk and/or prognosis of internal cancers. Populations living at high latitudes would probably benefit from moderately increasing their exposure to UVB to provide a good vitamin D status.
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PMID:Sun and sun beds: inducers of vitamin D and skin cancer. 1966 43

Because solar UV-radiation represents the most important environmental risk factor for the development of non-melanoma skin cancer, UV protection is important to prevent these malignancies. Consequently, public health campaigns were developed to improve the knowledge of the general population regarding the role of UV-radiation for the development of skin cancer. However, it has to be noted that vitamin D-mediated positive effects of UV light were not adequately considered in most of these campaigns, that often propose a strict 'no sun policy' without giving recommendations how to prevent vitamin D-deficiency. Under our living conditions, approximately 90% of all vitamin D needed by the human body has to be formed in the skin through the action of UV-B-radiation and it has been shown that strict sun protection causes vitamin D-deficiency. This dilemma represents a serious problem, for an association of vitamin D-deficiency and multiple independent diseases including various types of cancer, bone diseases, autoimmune diseases, infectious diseases, cardiovascular diseases and hypertension has now been reported in a large number of laboratory and epidemiologic investigations. Although further work is necessary to define an adequate vitamin D-status and adequate guidelines for UV-exposure, it is at present mandatory that guidelines for UV-exposure (e.g. in skin cancer prevention campaigns) consider these facts and give recommendations how to prevent vitamin D-deficiency. At present, most experts in the field agree that the evidence to date suggests that daily intake of 1000-2000 IU vitamin D could reduce the incidence of vitamin D-deficiency-related diseases with minimal risk in Europe, the US, and other countries. In this review, we analyze the present literature to help developing well-balanced guidelines on UV-protection that ensure an adequate vitamin D-status. These recommendations will hopefully protect us against vitamin D-deficiency without increasing the risk to develop UV-induced skin cancer.
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PMID:Skin cancer prevention and UV-protection: how to avoid vitamin D-deficiency? 1977 58

Vitamin D exerts its physiological functions on calcium and bone metabolism in humans through the active metabolite 1,25-dihydroxyvitamin D3(1,25(OH)2D3). The other spectrum of vitamin D activities includes important effects on cellular proliferation, differentiation and the immune system. These effects are mediated through the intracellularly located vitamin D receptor (VDR). VDR is a member of the steroid, estrogen and retinoid receptor gene family of proteins that mediate transcriptional activities of the respective ligands. The VDR complex binds in the nucleus to the vitamin D responsive element on the gene. Several polymorphisms of the vitamin D receptor (VDR) gene have been described including FokI in exon 2, BsmI and ApaI in intron 8 and TaqI in exon 9. Alterations in vitamin D-1,25 (OH)2D3 levels and polymorphisms of VDR gene have been shown to be associated with several malignant or autoimmune diseases such as sclerosis multiplex, breast cancer, diabetes mellitus, malignant melanoma, and psoriasis vulgaris. The effects of VDR gene polymorphisms including immunomodulation, stimulation of cellular differentiation and inhibition of proliferation make it a possible candidate for therapy of psoriasis as well as for the psoriasis gene modification. The objective of this article is to present the state-of-the-art in the VDR gene polymorphism research in psoriasis vulgaris.
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PMID:Vitamin D endocrine system and psoriasis vulgaris--review of the literature. 1981 18

To determine the relationship between 25(OH) vitamin D levels and non-melanoma skin cancer (NMSC), we performed a nested case-control study in ambulatory, elderly men enrolled in the Osteoporotic Fractures in Men (MrOS) Study. Health habit and medical history, including self-reported history of NMSC were recorded and 25(OH)D levels were measured on serum collected at baseline from a random sample of Caucasian MrOS subjects. Mean age (73 +/- 5), BMI, daily vitamin D and calcium intake were similar in the men with (n = 178) and without NMSC (n = 930), but higher levels of 25(OH)D were associated with a decreased risk of having a history of NMSC (P(trend) = 0.04). Men in the highest quintile of 25(OH)D (>30 ng/mL) had 47% lower odds of NMSC (95% CI: 0.30-0.93, p = 0.026) compared to those in the lowest quintile. Our results suggest that a diagnosis of NMSC is not a surrogate for adequate 25(OH)D levels or increased UV exposure, and high 25(OH)D levels may be associated with a reduced risk of NMSC.
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PMID:Inverse association between serum 25(OH) vitamin D levels and non-melanoma skin cancer in elderly men. 1992 45

The ultraviolet-B (UVB)-vitamin D-cancer hypothesis was proposed in 1980. Since then, several ecological and observational studies have examined the hypothesis, in addition to one good randomized, controlled trial. Also, the mechanisms whereby vitamin D reduces the risk of cancer have been elucidated. This report aims to examine the evidence to date with respect to the criteria for causality in a biological system first proposed by Robert Koch and later systematized by A. Bradford Hill. The criteria of most relevance are strength of association, consistency, biological gradient, plausibility/mechanisms and experimental verification. Results for several cancers generally satisfy these criteria. Results for breast and colorectal cancer satisfy the criteria best, but there is also good evidence that other cancers do as well, including bladder, esophageal, gallbladder, gastric, ovarian, rectal, renal and uterine corpus cancer, as well as Hodgkin's and non-Hodgkin's lymphoma. Several cancers have mixed findings with respect to UVB and/or vitamin D, including pancreatic and prostate cancer and melanoma. Even for these, the benefit of vitamin D seems reasonably strong. Although ecological and observational studies are not generally regarded as able to provide convincing evidence of causality, the fact that humanity has always existed with vitamin D from solar UVB irradiance means that there is a wealth of evidence to be harvested using the ecological and observational approaches. Nonetheless, additional randomized, controlled trials are warranted to further examine the link between vitamin D and cancer incidence, survival and mortality.
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PMID:How strong is the evidence that solar ultraviolet B and vitamin D reduce the risk of cancer?: An examination using Hill's criteria for causality. 2004 84

Indoor tanning has become increasingly popular over the past decades, despite evidence of an increased risk of melanoma and, possibly, nonmelanoma skin cancer. Tanning bed proponents cite the health benefits of vitamin D to support indoor tanning, including concerns that reduced vitamin D levels or certain vitamin D receptor polymorphisms may be associated with increased incidence of various cancers, including cutaneous melanoma. However, most tanning devices primarily emit ultraviolet A, which is relatively ineffective in stimulating vitamin D synthesis. Health benefits can be fully dissociated from the ultraviolet exposure risks with vitamin D supplementation, although optimal levels remain to be established. Indoor tanning represents an avoidable risk factor for skin cancer, and education of the general public as well as the enactment and stricter enforcement of indoor tanning legislation are a public health imperative.
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PMID:Tanning beds, skin cancer, and vitamin D: An examination of the scientific evidence and public health implications. 2013 9

Vitiligo is a disorder with complex causes and is a type of autoimmune disease in which the immune system targets the body's own pigment cells and tissues. Our aim is to present an overall view of the current remedies widely adopted for the treatment of vitiligo. Medical treatments target the immune system, and try to reverse the destruction. The goal is to restore the skin's color by restoring healthy melanocytes to the affected area. Apart from melanocytes, vitiligo autoantigens appear also on other cells. Even though antibodies to pigment cells are not an agent of vitiligo, the most valuable contribution is that anti-melanocyte antibody reactivity can help in identifying relevant antigens. T cells from vitiligo skin are highly reactive towards melanoma cells and serve as an effective source to treat melanoma and stays as a solution for vitiligo. There have been many treatments to cure vitiligo such as use of steroid creams, PUVA (psoralen and ultraviolet A light), narrow band UVB (ultraviolet B), various surgical techniques, vitamin D analogues and pseudocatalase. These treatments are subjected for undesired side effects whereas some herbal and natural treatments act against the immune system with no side effects.
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PMID:Current remedies for vitiligo. 2014 99

Malignant melanoma cells express the vitamin D receptor (VDR). However, some melanoma cell lines fail to respond to the antiproliferative effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). We reported previously that out of seven melanoma cell lines analyzed, three cell lines (MeWo, SK-Mel28, SM) respond to the antiproliferative effects of 1,25(OH)2D3, while the others (SK-Mel5, SK-Mel25, IGR, Meljuso) are resistant. It was the aim of this study to investigate whether epigenetic mechanisms are of importance for the abrogation of vitamin D signaling in vitamin D resistant melanoma cells. We used the histone deacetylase inhibitor (HDACI) trichostatin A (TSA) and the DNA methyltransferase inhibitor (DNMTI) 5-azacytidine (5-Aza) to elucidate the effects of protein acetylation and of DNA hypermethylation on 1,25(OH)2D3-induced effects on cell proliferation, respectively. Additionally we analyzed the expression of VDR microRNA in 1,25(OH)2D3-responding and resistant melanoma cells. TSA and 5-Aza exerted dose- and time-dependent antiproliferative effects on melanoma cell lines. Interestingly, combination therapy with 1,25(OH)2D3 and TSA exerted synergistic antiproliferative effects in a 1,25(OH)2D3-resistant melanoma cell line (IGR) (p<0.05). Combination therapy with 1,25(OH)2D3 and 5-Aza resulted in synergistic (MeWo after 72 h; p<0.05) or additive (other melanoma cell lines analyzed) antiproliferative effects. Additionally, we could show that VDR mRNA expression is relatively high in two of three 1,25(OH)2D3-responsive melanoma cells as compared to resistant cells, moreover this relatively high VDR expression is associated with low expression of miRNA125b in MeWo and SK-Mel28 cells. Our results suggest that the endogenous VDR mRNA level is inversely associated with expression of miRNA125b in melanoma cell lines analyzed. Moreover, miRNA125b may be involved in the regulation of VDR expression and in the resistance against 1,25(OH)(2)D(3) in melanoma cells. It can be speculated whether miRNA125b may be of prognostic importance and/or may represent a therapeutic target for malignant melanoma. Drugs that influence epigenetic mechanisms might be promising therapeutics for the treatment of metastasized malignant melanoma, alone or in combination with antiproliferative or cytotoxic agents such as 1,25(OH)2D3.
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PMID:VDR microRNA expression and epigenetic silencing of vitamin D signaling in melanoma cells. 2015 27

Intermittent sun exposure and sunburn are strong predictors of cutaneous malignant melanoma (CMM). On the other hand, melanomas may arise also in non-sun-exposed areas such as the vulva. However, little is known about a possible relationship between sun exposure and vulvar melanoma. Temporal and latitudinal dependencies of the incidence rates of vulvar melanoma were studied in comparison with those of CMM among Caucasians in Sweden, East Germany, USA and Victoria (Australia). The ratios of vulvar melanoma incidence rates to those of CMM tend to decrease with increasing CMM rates. The incidence rates of CMM have increased with time until recently, while those of vulvar melanoma have either decreased or remain constant. In USA vulvar melanoma incidence rates seem to increase from south to north, while for CMM incidence rates on sun exposed skin areas decrease from south to north. Comparison of latitudinal trends of the incidence rates of vulvar melanomas and CMM show opposite trends. Whenever CMM rates increase, either with time or with decreasing latitude (indicating increased sun exposure) the ratio of vulvar melanoma rates to CMM rates on exposed skin, seem to decrease. Thus, latitudinal trends seem to support the assumption that vulvar melanomas are not generated by UV radiation, and the possibility exists that solar UV radiation, probably via its role in vitamin D photosynthesis in exposed skin, may have a protective effect against vulvar melanoma and should be further investigated.
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PMID:Where the sun does not shine: is sunshine protective against melanoma of the vulva? 2035 7


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