Vitamin D Receptor Polymorphism and Cancer: An Update

Rai, Vikrant; Abdo, Joe; Agrawal, Swati; Agrawal, Devendra K.

doi:10.21873/anticanres.11784

Cited by 37 publications

(48 citation statements)

References 55 publications

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“…However, the biological functions of these SNPs are uncertain, and effects associated with them ascribed to haplotype connections or linkage to truly functional polymorphisms elsewhere in the VDR [41]. This is the case for the most studied VDR SNPs Apa1, Bsm1, Taq1, and Fok1 that in particular have been analyzed in relation to cancer, but with inconsistent results [12]. There are only a few studies on these VDR SNPs and mortality, and as for cancer the results are non-conclusive.…”

Section: Discussionmentioning

confidence: 99%

“…Another approach is the Mendelian randomization (MR) procedure [5], and there are several single nucleotide polymorphisms (SNPs) related to enzymes needed for activation, transport and breakdown of vitamin D, as well as in the VDR. However, the results have not consistently been in favour of vitamin D. Thus, SNPs related to synthesis and breakdown of 25 Similarly, there have been numerous studies on VDR SNPs, in particular regarding cancer, but also these have shown conflicting results [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms in the vitamin D system and mortality - The Tromsø study

Jorde

Wilsgaard

Grimnes

2019

Preprint

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Background and objectiveVitamin D deficiency is associated with diabetes, cancer, immunological and cardiovascular diseases as well as increased mortality. It has, however, been difficult to show a causal relation in randomized, controlled trials. Mendelian randomization studies provide another option for testing causality, and results indicate relations between the serum 25hydroxyvitamin D (25(OH)D) level and some diseases, including mortality. We have from the Tromsø Study in 2012 published non-significant relations been vitamin D related single nucleotide polymorphisms (SNPs) and mortality, but have since then genotyped additional subjects, the observation time is longer and new SNPs have been included. Methods Genotyping was performed for SNPs in the NADSYN1, CYP2R1, VDR, CUBILIN and MEGALIN genes in 11 897 subjects who participated in the fourth survey of the Tromsø Study in 1994-1995. Serum 25(OH)D levels were measured in 6733 of these subjects. A genotype score based on SNPs in the NADSYN1 and CYP2R1 genes (related to the serum 25(OH)D level) and serum 25(OH)D percentile groups were created. Mortality data was updated till end of March 2017 and survival analysed with Cox regression adjusted for sex and age. ResultsDuring the observation period 5491 subjects died. The genotype score and the serum 25(OH)D percentile groups were (without Bonferroni correction) significantly related to mortality in favour of high serum 25(OH)D. None of the SNPs in the VDR or MEGALIN genes were related to mortality. However, for the rs12766939 in the CUBILIN gene with the major homozygote as reference, the hazard ratio for mortality for the minor homozygote genotype was 1.17 (1.06 -1.29), P < 0.002. This should be viewed with caution, as rs12766939 was not in Hardy-Weinberg equilibrium. ConclusionOur study confirms a probable causal but weak relation between serum 25(OH)D level and mortality. The relation between rs12766939 and mortality needs confirmation in more homogenous cohorts.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the vitamin D system and mortality - The Tromsø study

Jorde

Wilsgaard

Grimnes

2019

Preprint

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“… 49 Taq I polymorphism in MM is associated with an increased risk of associated disease and has prognostic value. 53 In AA, Bsm I and Taq I are associated with a poor prognosis. 55 …”

Section: Discussionmentioning

confidence: 99%

“…In MM, the TT genotype of Taq I and the mutated C allele of Taq I have a significant relationship with increased risk of disease. 53 Another study reported that Fok I polymorphism inhibited tumor growth in MM patients. 49 A study has indicated that DCs in MM patients have anabnormal function and that their defects are related to tumorigenicity in cancer.…”

Section: Other Blood Disordermentioning

confidence: 99%

Vitamin D and its receptor polymorphisms: New possible prognostic biomarkers in leukemias

et al. 2018

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Several factors such as chromosomal translocations, gene mutations, and polymorphisms are involved in the pathogenesis of leukemia/lymphoma. Recently, the role of vitamin D (VD) and vitamin D receptor (VDR) polymorphisms in hematologic malignancies has been considered. In this review, we examine the possible role of VD levels, as well as VDR polymorphisms as prognostic biomarkers in leukemia/lymphoma. Relevant English language literature were searched and retrieved from Google Scholar search engine (1985-2017). The following keywords were used: vitamin D, vitamin D receptor, leukemia, lymphoma, and polymorphism. Increased serum levels of VD in patients with leukemia are associated with a better prognosis. However, low VD levels are associated with a poor prognosis, and VDR polymorphisms in various leukemias can have prognostic value. VD biomarker can be regarded as a potential prognostic factor for a number of leukemias, including acute myeloblastic leukemia (AML), chronic lymphoblastic leukemia (CLL), and diffuse large B-cell lymphoma (DLBCL). There is a significant relationship between different polymorphisms of VDR (including Taq I and Fok I) with several leukemia types such as ALL and AML, which may have prognostic value.

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“…In both mechanisms of action the participation of the vitamin D receptor (VDR) has been described [5]. This receptor is a member of the nuclear family of receptors and it is distributed in many normal and tumor tissues [6,7]. When calcitriol binds to VDR, it heterodimerizes with the nuclear retinoid X receptor (RXR) and this complex (calcitriol-VDR-RXR) subsequently recruits cofactors to the vitamin D response elements (VDRE) in the promoter region of target genes [3,5].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of a novel analog of calcitriol and its biological evaluation as antitumor agent

Ferronato

Obiol

Alonso

et al. 2019

The Journal of Steroid Biochemistry and Molecular Biology

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Calcitriol analogs have shown promising potential as compounds to be used in cancer chemotherapy. This report presents the synthesis of a novel vitamin D derivative with an amide and a carboxyl group in its side chain, called ML-344. In addition, we report its in vitro antitumor activity and its in vivo calcemic effects. We demonstrate that the analog decreases cell viability and retards cell migration of different breast, glioblastoma and head and neck cancer cell lines. Additionally, unlike calcitriol, ML-344 does not display citotoxicity to the murine non-malignant mammary cells and human astrocytes. In concordance with the antimigratory effects found in breast cancer cells, ML-344 decreased the invasive capacity and induced a rearrangement of the actin cytoskeleton in the LM3 breast cancer cell line. In relation to the in vivo studies, the analog did not cause hypercalcemic effects in CF1 mice administered daily at 5 μg/Kg of body weight during a period of 264 h. Finally, computational studies were performed to evaluate the potential binding of the analog to the vitamin D receptor and the in silico assays showed that ML-344 is able to bind to VDR with interesting particularities and greater affinity than calcitriol. Altogether, these results suggest that ML-344 has a promising potential as an antitumor agent with a differential effect between tumor and non-malignant cells.

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Vitamin D Receptor Polymorphism and Cancer: An Update

Abstract: Abstract. Background: Vitamin D mediates its action via vitamin D receptor (VDR) and is involved in a wide

Cited by 37 publications

References 55 publications

Polymorphisms in the vitamin D system and mortality - The Tromsø study

Polymorphisms in the vitamin D system and mortality - The Tromsø study

Vitamin D and its receptor polymorphisms: New possible prognostic biomarkers in leukemias

Synthesis of a novel analog of calcitriol and its biological evaluation as antitumor agent

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