Vitamin D Receptor Polymorphisms Are Associated with Reduced Esophageal Vitamin D Receptor Expression and Reduced Esophageal Adenocarcinoma Risk

Janmaat, Vincent T.; Winkel, Anouk van de; Peppelenbosch, Maikel P.; Spaander, Manon; Uitterlinden, André G.; Pourfarzad, Farzin; Tilanus, Hugo W.; Rygiel, Agnieszka Magdalena; Moons, Leon M.G.; Arp, Pascal P.; Krishnadath, Kausilia K.; Kuipers, Ernst J.; Laan, Luc J. W. van der

doi:10.2119/molmed.2012.00336

Cited by 13 publications

(12 citation statements)

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“…Allele frequencies and N total/N deaths for each individual genotype can be found in the Table S1. Allele frequencies and N total/N deaths for each individual genotype can be found in the Table S1. regarded as a negative TF, and although specific information for melanomas is lacking, in esophageal adenocarcinomas the rs1989969-T allele (responsible for greater risk of melanoma death in our study among those with high UVB) was linked to reduction in VDR expression (Janmaat et al, 2015).…”

Section: Discussionmentioning

confidence: 53%

“…The significant rs1989969 is located in an evolutionary conserved region upstream of the translation start, and T‐alleles are responsible for the differential binding of the transcription factor (TF) GATA‐1 to the VDR gene. 33 GATA‐1 is generally regarded as a negative TF, and although specific information for melanomas is lacking, in esophageal adenocarcinomas the rs1989969‐T allele (responsible for greater risk of melanoma death in our study among those with high UVB) was linked to reduction in VDR expression (Janmaat et al., ).…”

Section: Discussionmentioning

confidence: 59%

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The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival

Orlow

Shi

Kanetsky

et al. 2017

Pigment Cell Melanoma Res

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Evidence on the relationship between the vitamin D pathway and outcomes in melanoma is growing, although it is not always clear. We investigated the impact of measured levels of sun exposure at diagnosis on associations of vitamin D receptor gene (VDR) polymorphisms and melanoma death in 3336 incident primary melanoma cases. Interactions between six SNPs and a common 3'-end haplotype were significant (p < .05). These SNPs, and a haplotype, had a statistically significant association with survival among subjects exposed to high UVB in multivariable regression models and exerted their effect in the opposite direction among those with low UVB. SNPs rs1544410/BsmI and rs731236/TaqI remained significant after adjustment for multiple testing. These results suggest that the association between VDR and melanoma-specific survival is modified by sun exposure around diagnosis, and require validation in an independent study. Whether the observed effects are dependent or independent of vitamin D activation remains to be determined.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 59%

The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival

Orlow

Shi

Kanetsky

et al. 2017

Pigment Cell Melanoma Res

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“…A limitation of our study was that the protein levels of VDR were not determined because of the limited counts of PBMCs. However, previous studies have demonstrated that the mRNA and protein levels of VDR in various tissues, such as placental endothelium, squamous epithelium, and parathyroid cells, exhibited similar trends without in vivo or in vitro intervention . Further studies are needed to validate the concordant results between the mRNA and protein levels of VDR in patients with AA.…”

Section: Discussionmentioning

confidence: 92%

Decreased expression of vitamin D receptor may contribute to the hyperimmune status of patients with acquired aplastic anemia

et al. 2015

European J of Haematology

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Acquired aplastic anemia (AA) is an immune-mediated bone marrow failure syndrome. 1α,25-Dihydroxyvitamin D3 [1,25(OH)2 D3 ], the biologically active metabolite of vitamin D, is a critical modulator of immune response via binding with vitamin D receptor (VDR). Previous studies have established that 1,25(OH)2 D3 and VDR were involved in the pathogenesis of some autoimmune diseases. In this study, we evaluated the involvement of 1,25(OH)2 D3 and VDR on T-cell responses in AA. Plasma 25(OH)D3 levels were comparable between patients with AA and healthy controls. Surprisingly, VDR mRNA was significantly lower in untreated patients with AA than in healthy controls. Subsequent in vitro experiments revealed that 1,25(OH)2 D3 treatment suppressed the proliferation of lymphocytes and inhibited the secretion of interferon-γ, tumor necrosis factor-α, and interleukin-17A, meanwhile promoting the production of transforming growth factor-β1 in patients with AA. Moreover, 1,25(OH)2 D3 inhibited the differentiation of type 1 and Th17 cells but induced the differentiation of type 2 and regulatory T cells. Interestingly, VDR mRNA was elevated in healthy controls after 1,25(OH)2 D3 treatment, but not in patients with AA. In conclusion, decreased expression of VDR might contribute to the hyperimmune status of AA and appropriate vitamin D supplementation could partly correct the immune dysfunction by strengthening signal transduction through VDR in patients with AA.

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“…[ 34 , 37 – 39 ] VDR expression is upregulated in BE compared with normal esophageal mucosa,[ 34 , 38 ] suggesting that BE may be more sensitive than normal esophageal mucosa to the effects of calcitriol, the active form of vitamin D. Recent data also suggest that genetic variations in VDR are linked to reduced EAC risk. [ 40 ] Clinically, low vitamin D levels have been associated with insulin resistance and metabolic syndrome,[ 41 ] both of which are common in BE patients. [ 29 , 42 ] Moreover, vitamin D deficiency is associated with an increased risk, as well as worse outcomes, in other cancers.…”

Section: Discussionmentioning

confidence: 99%

A nonrandomized trial of vitamin D supplementation for Barrett’s esophagus

Cummings

Thota

Willis³

et al. 2017

PLoS ONE

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BackgroundVitamin D deficiency may increase esophageal cancer risk. Vitamin D affects genes regulating proliferation, apoptosis, and differentiation and induces the tumor suppressor 15-hydroxyprostaglandin dehydrogenase (PGDH) in other cancers. This nonrandomized interventional study assessed effects of vitamin D supplementation in Barrett’s esophagus (BE). We hypothesized that vitamin D supplementation may have beneficial effects on gene expression including 15-PGDH in BE.MethodsBE subjects with low grade or no dysplasia received vitamin D3 (cholecalciferol) 50,000 international units weekly plus a proton pump inhibitor for 12 weeks. Esophageal biopsies from normal plus metaplastic BE epithelium and blood samples were obtained before and after vitamin D supplementation. Serum 25-hydroxyvitamin D was measured to characterize vitamin D status. Esophageal gene expression was assessed using microarrays.Results18 study subjects were evaluated. The baseline mean serum 25-hydroxyvitamin D level was 27 ng/mL (normal ≥30 ng/mL). After vitamin D supplementation, 25-hydroxyvitamin D levels rose significantly (median increase of 31.6 ng/mL, p<0.001). There were no significant changes in gene expression from esophageal squamous or Barrett’s epithelium including 15-PGDH after supplementation.ConclusionBE subjects were vitamin D insufficient. Despite improved vitamin D status with supplementation, no significant alterations in gene expression profiles were noted. If vitamin D supplementation benefits BE, a longer duration or higher dose of supplementation may be needed.

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Vitamin D Receptor Polymorphisms Are Associated with Reduced Esophageal Vitamin D Receptor Expression and Reduced Esophageal Adenocarcinoma Risk

Abstract: Cite this article as: Janmaat VT, et al. (2015) Vitamin D receptor polymorphisms are associated with reduced esophageal vitamin D receptor expression and reduced esophageal adenocarcinoma risk. Mol.

Cited by 13 publications

References 46 publications

The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival

The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival

Decreased expression of vitamin D receptor may contribute to the hyperimmune status of patients with acquired aplastic anemia

A nonrandomized trial of vitamin D supplementation for Barrett’s esophagus

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