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

It has been hypothesized that polymorphisms in the vitamin D receptor (VDR) gene affect the risk of developing melanoma. However, results often are conflicting, and no meta-analysis has been performed to date on published data. Six studies (cases, 2152; controls, 2410) that investigated the association between 5 VDR polymorphisms (TaqI, FokI, BsmI, EcoRV, and Cdx2) and the risk of melanoma were retrieved and analyzed. The model-free approach was applied to meta-analyze these molecular association studies. Available data suggested a significant association between the BsmI VDR polymorphism and melanoma risk (pooled odds ratio [OR], 1.30; 95% confidence interval [CI], 1.11-1.53; P= .002; heterogeneity Cochran Q test, P> .1), and the population-attributable risk was 9.2%. In contrast, the FokI polymorphism did not appear to be associated with such risk (OR, 1.09; 95% CI, 0.99-1.21; P= .07; heterogeneity Cochran Q test, P> .1). For the TaqI and the EcoRV polymorphisms, significant between-study heterogeneity did not support genotype data pooling. Only 1 study investigated the Cdx2 variant, and the findings were negative. Current evidence is in favor of an association between 1 VDR gene polymorphism (BsmI) and the risk of developing melanoma. The current findings prompt further investigation on this subject and indirectly support the hypothesis that sun exposure may have an antimelanoma effect through activation of the vitamin D system.
 ...
PMID:Vitamin D receptor polymorphisms and the risk of cutaneous melanoma: a systematic review and meta-analysis. 1881 36

Ultraviolet radiation (UVR) is an essential risk factor for the development of premalignant skin lesions as well as of melanoma and non-melanoma skin cancer. UVR exerts many effects on the skin, including tanning, carcinogenesis, immunomodulation, and production of vitamin D. Vitamin D (vit D) is important in the maintenance of healthy bones as well as other purported beneficial effects, amongst which is the potential for reducing risk of malignancy--though oral supplementation is fully capable of maintaining systemic levels. The known medical harm from UV exposure relates primarily to cancer of the skin--the most common organ in man to be affected by cancer. In this review, we summarize the knowledge about the ultraviolet (UV) response in regards to inflammation, immunosuppression, carcinogenesis and the tanning response. We also discuss vit D and UV, as well as public health implications of tanning behavior and commercial interests related to the promotion of UV exposure. As the most ubiquitous human carcinogen, UVR exposure represents both a challenge and enormous opportunity in the realm of skin cancer prevention.
Pigment Cell Melanoma Res 2008 Oct
PMID:UV and pigmentation: molecular mechanisms and social controversies. 1905 42

Controversy continues over the carcinogenic properties of tanning beds. The tanning industry "sells" tanning beds as a safe alternative to UV exposure for both tanning as well as vitamin D biosynthesis. But, how safe are tanning beds? Epidemiologic data - incomplete and unsatisfactory - suggests that tanning beds are not safer than solar ultraviolet radiation and that they may have independent effects from solar exposure that increase risk for melanoma.
Pigment Cell Melanoma Res 2008 Oct
PMID:Are tanning beds "safe"? Human studies of melanoma. 1882 56

The results of Primary Prevention programs, aiming at the decrease of melanoma incidence, were less encouraging than those of Secondary prevention which aims at an early diagnosis of malignant melanoma. Australia was the country with the best results obtained in both Prevention strategies, especially in avoiding intense, though intermittent, UV exposure. The success of these programs encouraged health authorities to initiate their application to other disorders. New sunscreens containing substances correcting the UV-damaged DNA may offer a promising result in the decades to come. However, so far no one epidemiological study has proved the prevention of malignant melanoma with the use of sun protecting agents. A meta-analysis verified the connection between melanoma and solarium use. The protective role of vitamin D in the development of prostate, breast and colon cancer was shown in a meta-analysis. The authors, however, suggest that fair-skinned persons should take oral supplementation of vitamin D, instead of exposing themselves to the sun. The Hellenic Society of Dermatology and Venereology published the results of 5-year-prevention programs in Greece. Their favorable results in the early diagnosis of melanoma justify an intense continuation of these efforts.
 ...
PMID:Prevention of malignant melanoma. 1892 59

Pregna-5,7-dienes and their hydroxylated derivatives can be formed in vivo when there is a deficiency in 7-dehydrocholesterol (7-DHC) Delta-reductase function, e.g., Smith-Lemli-Opitz syndrome (SLOS). Ultraviolet B (UVB) radiation induces photoconversion of 7-DHC to vitamin D3, lumisterol3 and tachysterol3. Two epimers (20R and 20S) of pregna-5,7-diene-3beta,17alpha,20-triol (4R and 4S, respectively) were synthesized and their UVB photo-conversion products identified as corresponding 9,10-secosteroids with vitamin D-like and tachysterol-like structures, and 5,7-dienes with inverted configuration at C-9 and C-10 (lumisterol-like). The number and character of the products and the dynamics of the process were dependent on the UVB dose. At high UVB doses, the formation of multiple oxidized derivatives of the primary products, and the formation of 5,7,9(11)-triene, were observed. The production of vitamin D-like, tachysterol-like and lumisterol-like derivatives was also observed in human skin treated with 4R and 4S, and subjected to UV irradiation, as shown by RP-HPLC. Newly synthesized compounds inhibited melanoma growth in dose dependent manner, and some of them showed equal or higher potency than 1,25(OH)2D3. In summary, we have characterized for the first time the products of UV induced conversion of pregna-5,7-diene-3beta,17alpha,20-triols and documented that the newly synthesized compounds have antiproliferative properties against melanoma cells.
 ...
PMID:Photo-conversion of two epimers (20R and 20S) of pregna-5,7-diene-3beta, 17alpha, 20-triol and their bioactivity in melanoma cells. 1902 13

Vitamin D has a positive impact on our overall health. Also there are a few conditions with strong evidence for a protective effect of vitamin D, such as bone diseases, internal cancers, multiple sclerosis, hypertension and DM type 1. Skin is the major source of vitamin D through the action of UVB light on keratinocytes, although the biologically active form of vitamin D is not exclusively produced in the kidney but also in prostate, colon, skin and osteoblast where it acts as an autocrine or paracrine hormone. In the past decade raising incidence of skin cancers, especially melanoma and its connection with sun exposure lead to a sun protection policies and practices as part of the public health campaigns. The question is how much solar UV exposure is adequate to maintain the balance between the risk and the benefit. We as dermatologists have to raise public awareness of the potential health effects from excessive exposure to UV radiation but also we have to be aware that adequate blood level of vitamin D is necessary for optimal health. So future recommendation on sun protection have to balance between the risk and benefits of sun exposure, as well as to promote vitamin D supplementation as a safe alternatives in high risk population.
 ...
PMID:Vitamin D--the true and the false about vitamin D. 1913 20

Epidemiological studies suggest a relationship between suntanning habits and high risk of malignant melanoma (MM). The incidence of MM is increased during the last 40 years. Sun exposure is highly prevalent in all age groups, especially among young and it is influenced by certain believes and attitudes towards suntanning and stimulated by peer pressure and aesthetic references. What is the cause of higher incidence of MM? Is it only trend and attitudes towards suntanning? A prototype of a young female of 21st century is attractive, slim, with bronze complexion, dresses in the bathing suit, whereas the lady of the 19th is pale, dressed in white dress and with hat or sunshade that protects face and hair from the sun. When did social mores and medical knowledge about sun exposure change? A critical interplay occurred between the end of 19th century and the start of the 20th century with significant success of phototherapy and the growing popularity of sunbathing which reflected number of social changes. During the same time of invigoration of sun exposure, appeared the first reports about correlation between sunlight and skin cancer, but without significant repercussion on medical profession and therefore without knowledge of the public. The 1920s and 1930s were highlighted with the great discovery that ultraviolet wavelengths less than 313 nm played the role in vitamin D synthesis which prevents rickets. Numerous other medical benefits were soon attributed to the sunlight. Finally, the cancerogenity of UV light came to attention when scientist succeeded in induction of skin cancer in rodents after UV light exposure. The etiology of sunlight in development of skin cancer was mentioned in scientific articles and public magazines in 1940s and 1950s. Over the decades the message that sunlight exposure leads to increased risk of skin cancer, reach the public. But despite the knowledge, even at present people believe that tan person looks healthier. Additional and continuous educational campaigns are needed for changing people's behavior.
 ...
PMID:Trends, habits and attitudes towards suntanning. 1914 Feb 78

Cutaneous malignant melanoma (CMM) has been increasing at a steady exponential rate in fair-skinned, indoor workers since before 1940. A paradox exists between indoor and outdoor workers because indoor workers get three to nine times less solar UV (290-400 nm) exposure than outdoor workers get, yet only indoor workers have an increasing incidence of CMM. Thus, another "factor(s)" is/are involved that increases the CMM risk for indoor workers. We hypothesize that one factor involves indoor exposures to UVA (321-400 nm) passing through windows, which can cause mutations and can break down vitamin D(3) formed after outdoor UVB (290-320 nm) exposure, and the other factor involves low levels of cutaneous vitamin D(3). After vitamin D(3) forms, melanoma cells can convert it to the hormone, 1,25-dihydroxyvitamin D(3), or calcitriol, which causes growth inhibition and apoptotic cell death in vitro and in vivo. We measured the outdoor and indoor solar irradiances and found indoor solar UVA irradiances represent about 25% (or 5-10 W/m(2)) of the outdoor irradiances and are about 60 times greater than fluorescent light irradiances. We calculated the outdoor and indoor UV contributions toward different biological endpoints by weighting the emission spectra by the action spectra: erythema, squamous cell carcinoma, melanoma (fish), and previtamin D(3). Furthermore, we found production of previtamin D(3) only occurs outside where there is enough UVB. We agree that intense, intermittent outdoor UV overexposures and sunburns initiate CMM; we now propose that increased UVA exposures and inadequately maintained cutaneous levels of vitamin D(3) promotes CMM.
 ...
PMID:Increased UVA exposures and decreased cutaneous Vitamin D(3) levels may be responsible for the increasing incidence of melanoma. 1915 43

Data suggest that vitamin D intake may have chemopreventive efficacy against melanoma, but there have been no published epidemiologic studies examining the association between vitamin D intake and melanoma risk in a large prospective cohort. We examined whether dietary and supplemental vitamin D intake was associated with melanoma risk among 68,611 men and women who were participants of the Vitamins and Lifestyle cohort study. Participants reported dietary vitamin D intake over the past year and 10-year use of multivitamin and individual vitamin D supplements on a baseline questionnaire. After follow-up through 2006, 455 incident melanomas were identified through linkage to the Surveillance, Epidemiology, and End Results cancer registry. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for vitamin D intake after adjustment for melanoma risk factors. Compared with the lowest quartile, we did not detect a risk reduction of melanoma in the highest quartiles of dietary vitamin D intake (RR=1.31, CI=0.94-1.82), 10-year average supplemental vitamin D intake (RR=1.13, CI=0.89-1.43), or combined dietary and supplemental intake (1.05, CI=0.79-1.40). In this large prospective cohort, we did not find an association between vitamin D intake and melanoma risk.
 ...
PMID:A cohort study of vitamin D intake and melanoma risk. 1952 3

Cholesterol is important for membrane stability and is the key substrate for the synthesis of steroid hormones and vitamin D. Furthermore, it is a major component of the lipid barrier in the stratum corneum of the human epidermis. Considering that steroid hormone synthesis is taking place in epidermal melanocytes, we tested whether downstream oestrogen receptor/cAMP signalling via MITF/tyrosine hydroxylase/tyrosinase/pigmentation could be possibly modulated by cholesterol. For this purpose, we utilized human primary melanocyte cell cultures and human melanoma cells with different pigmentation capacity applying immunofluorescence, RT-PCR, Western blotting and determination of melanin content. Our in situ and in vitro results demonstrated that melanocytes can synthesize cholesterol via HMG-CoA reductase and transport cholesterol via LDL/Apo-B100/LDLR. Moreover, we show that cholesterol increases melanogenesis in these cells and in human melanoma cells of intermediate pigmentation (FM55) in a time- and dose-dependent manner. Cellular cholesterol levels in melanoma cells with different pigmentation patterns, epidermal melanocytes and keratinocytes do not differ except in the amelanotic (FM3) melanoma cell line. This result is in agreement with decreasing cholesterol content versus increasing pigmentation in melanosomes. Cholesterol induces cAMP in a biphasic manner i.e. after 30 min and later after 6 and 24 h, meanwhile protein expression of oestrogen receptor beta, CREB, MITF, tyrosine hydroxylase and tyrosinase is induced after 72 h. Taken together, we show that human epidermal melanocytes have the capacity of cholesterol signalling via LDL/Apo-B100/LDL receptor and that cholesterol under in vitro conditions increases melanogenesis.
 ...
PMID:Cholesterol regulates melanogenesis in human epidermal melanocytes and melanoma cells. 1946 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>