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1、1Vitamin D Receptor Polymorphism Linked to MelanomaPADOVA, Italy, Sept. 22 - A polymorphism in the vitamin D receptor significantly increased the risk of melanoma, a meta-analysis of published data showed. Source reference: Mocellin S, Nitti D “Vitamin D receptor polymorphisms and the risk of cutane
2、ous melanoma“ Cancer 2008; DOI: 10.1002/cncr.23867.Individuals with the BsmI polymorphism had a 30% increase in the odds ratio for melanoma, Simone Mocellin, M.D., Ph.D., and Donato Nitti, M.D., of the University of Padova, reported online in Cancer. Another vitamin D receptor polymorphism previousl
3、y implicated in melanoma had no association with the cancer. Data were inconclusive regarding three additional polymorphisms. “Current evidence is in favor of the association between one vitamin D receptor gene polymorphism and the risk of melanoma development, although further work will be necessar
4、y to validate the risk identified in the current meta-analysis,“ the authors concluded. A growing body of evidence suggests that vitamin D - specifically 1,25- dihydroxycholecaliciferol (1,25OH2D3) - has significant protective effects against cancer. Much of the interest in vitamin Ds anticancer pot
5、ential centers on its role as a transcription factor involved in regulating cell growth, differentiation, and apoptosis, the authors said. Epidemiologic evidence has suggested an inverse association between sun exposure, serum levels of 1,25OH2D3, and vitamin D intake and the risk of developing or s
6、urviving cancer, they continued. “Because this vitamin exerts its function on engagement of its receptor . it is likely that polymorphisms of this nuclear hormone receptor family member affect the ability of interacting with its ligand, which ultimately would lead to different levels of vitamin D bi
7、ologic activity,“ said Drs. Mocellin and Nitti. Studies of specific polymorphisms have yielded conflicting results, and the total body of data had not been examined by meta-analytic techniques, they added. In an effort to fill in some of the gaps in the information, the authors analyzed data from si
8、x studies that investigated associations between melanoma and five vitamin D polymorphisms: TaqI, FokI, BsmI, EcoRV, and Cdx2. Collectively, the studies comprised 2,152 cases and 2,410 controls. Three of the six studies investigated the BsmI restriction fragment length polymorphism. The studies demo
9、nstrated homogeneity in three different odds ratio 2analyses. Logistic regression analysis suggested a significant association between the polymorphism and melanoma (P=0.02). A pooled analysis of genotype data provided further evidence of the association (P=0.002). Several investigators had proposed
10、 the FokI polymorphism as a contributor to melanoma risk. Two of four studies that examined the polymorphism found an association. However, meta-analysis failed to reveal a significant role for the polymorphism in melanoma risk. Data for the remaining three polymorphisms could not be analyzed adequa
11、tely because of conflicting findings or between-study heterogeneity that precluded meta- analysis. The authors said their findings are consistent indirectly with the hypothesis that the BsmI polymorphism alters interaction between 1,25OH2D3 and the vitamin D receptor, thereby reducing 1,25OH2D3 leve
12、ls or activity and increasing vulnerability to melanoma. They pointed out, however, that there is no current evidence of a functional effect of the polymorphism on vitamin D metabolism or the vitamin D receptor. They also noted that “a significant limitation of the current meta-analysis is that the
13、results could not be adjusted by patient characteristics (eg. age, sex), environmental factors (eg. sun exposure, dietary vitamin D intake), or any other melanoma risk factors (eg. phototype, skin/eye color). Conversely, only an individual patient data meta-analysis could address this issue,“ they said. 1. In the current analysis, how many vitamin D receptor polymorphisms had significant associations with melanoma risk? a.One b.Three c.All five d.None of them2. People with the BsmI polymorphism had an increased risk of melanoma. True or False?
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