Vitamin D Receptor Polymorphisms in Differentiated Thyroid Carcinoma

Penna-Martinez, Marissa; Ramos-Lopez, Elizabeth; Stern, Julienne; Hinsch, Nora; Hansmann, Martin‐Leo; Selkinski, I.; Grünwald, Frank; Vorländer, Christian; Wahl, R. A.; Bechstein, Wolf O.; Zeuzem, Stefan; Holzer, Katharina; Badenhoop, Klaus

doi:10.1089/thy.2008.0388

Cited by 60 publications

(63 citation statements)

References 36 publications

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“…The BsmI or FokI SNPs in VDR have been associated with breast, bladder, renal, carcinoma, and cutaneous malignant melanoma and nonmelanoma skin cancer (Mittal et al, 2007;Gandini et al, 2009;Tang et al, 2009;Arjumand et al, 2012). These polymorphisms were also recognized as risk factors of hepatocellular, head and neck, thyroid, prostate, and colorectal cancers (Liu et al, 2005;Mishra et al, 2005;Bai et al, 2009Bai et al, , 2012Penna-Martinez et al, 2009;Falleti et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor Gene BsmI and FokI Polymorphisms in Relation to Ovarian Cancer Risk in the Polish Population

Mostowska

Sajdak²,

Pawlik³

et al. 2013

Genetic Testing and Molecular Biomarkers

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Background: The role of vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) in ovarian cancer has been studied in various populations; however, these results are discordant between different ethnicities. Method: Using the polymerase chain reaction-restriction fragment length polymorphism method, we studied the prevalence of the VDR FokI (rs2228570) and BsmI (rs1544410) SNPs in women with ovarian cancer (n = 168) and controls (n = 182) in a Polish population.

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Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor Gene BsmI and FokI Polymorphisms in Relation to Ovarian Cancer Risk in the Polish Population

Mostowska

Sajdak²,

Pawlik³

et al. 2013

Genetic Testing and Molecular Biomarkers

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“…In addition, patients with 25(OH) D levels < 46.2 nmol/L (median) had significantly higher risk of advanced stage and lymph node metastasis after adjustment [17]. Penna-Martinez et al showed lower serum 1,25(OH) 2 D levels in 172 patients with DTC as compared to 321 controls, although there were no differences in 25(OH)D levels, and an association between VDR polymorphism and the risk of follicular thyroid cancer [21]. Later, the same authors revealed an association between low 25(OH)D and 1,25(OH) 2 D levels and DTC in patients with certain CYP24A1 haplotypes [22].…”

Section: Vitamin D and Thyroidmentioning

confidence: 98%

Low Vitamin D Status Is Not Associated With Thyroid Cancer Risk

Kim

2016

J Endocrinol Metab

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Background: Low vitamin D status has been known to be associated with the increased prevalence and worse prognosis of several cancers. The aim of this study was to investigate the correlation between vitamin D insufficiency and the risk of malignancy of thyroid nodules and the prognosis of differentiated thyroid cancers (DTCs). Methods:This cross-sectional study included a total of 410 patients who submitted to simultaneous measurements of serum 25-hydoxyvitamin D (25(OH)D) and ultrasonography-guided fine-needle aspiration for thyroid nodules during the period from March 2005 to June 2009. Levels of serum free thyroxine, thyroid stimulating hormone, anti-thyroid antibodies, parathyroid hormone (PTH), calcium, and phosphorus were also measured. Vitamin D insufficiency was defined as a serum 25(OH)D level < 75 nmol/L. In addition, the clinicopathologic characteristics of 34 patients who underwent thyroidectomy for DTC were analyzed retrospectively. Results:The prevalence of vitamin D insufficiency was 40.2%. Serum 25(OH)D levels and the prevalence of vitamin D insufficiency showed no significant differences between benign (n = 366) and malignant (n = 44, 10.7%) thyroid nodules. Serum 25(OH)D levels showed a negative correlation only with serum PTH levels after adjusting for age, sex, body mass index, and sampling season. Among DTC patients, vitamin D insufficiency was not associated with disease stage or any other prognostic features.Conclusions: Vitamin D insufficiency was not associated with the development of thyroid cancer or the prognostic characteristics of DTC.

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“…Penna-Martinez et al saw no correlation of these levels with thyroid cancer patients compared to healthy controls but did find a lower mean 1,25(OH)2D3 level in thyroid cancer patients compared to healthy controls (20). Unfortunately, there is no description of calcium status, parathyroid, or renal function that would be important given the rapid and dynamic regulation of 1,25(OH)2D3 levels.…”

Section: Figmentioning

confidence: 98%

“…A more recent study by Penna-Martinez et al evaluated the presence of VDR gene polymorphisms in blood samples of patients with differentiated thyroid carcinoma (20). There was a positive correlation of the ff FokI polymorphism with follicular thyroid cancer but not PTC relative to the frequency found in healthy controls.…”

Section: Figmentioning

confidence: 99%

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Thyroid Cancer Resistance to Vitamin D Receptor Activation Is Associated with 24-Hydroxylase Levels But Not theffFokI Polymorphism

Sharma

Fretwell

Crees

et al. 2010

Thyroid

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Background: The vitamin D receptor (VDR) has been studied as a novel target for cancer therapy in many tissue types as VDR ligands decrease cell proliferation in vitro and decrease tumor growth in vivo in sensitive cells. The objective of this study was to analyze the response to VDR agonist therapy in a panel of validated thyroid cancer cells and assess genetic markers predicting sensitivity and resistance to calcitriol and the noncalcemic analog DP006. Methods: Thyroid cancer cell lines were analyzed for VDR and RXR protein by Western blot. Cell growth after VDR agonist treatment (calcitriol or DP006) was assessed after 6 days of treatment by viable cell assay. To investigate calcitriol/DP006 resistance in VDR-expressing cells, the VDR was sequenced and 1-a and 24-hydroxylase mRNA expression was assessed. Results: VDR protein was variably expressed in the thyroid cancer cell lines and its presence was not sufficient for decreased viable cell count in response to calcitriol or DP006. The most sensitive cells (TPC1) have an ff FokI VDR polymorphism and the most resistant cells (HTh7 and 8505C) have an FF FokI VDR. This is a unique finding given that the balance of the literature of VDR polymorphisms describes an association of the ff FokI polymorphism with cancer risk and/or decreased VDR transactivation. 1-a and 24-hydroxylase mRNA expression before and after VDR agonist therapy was examined. 1-a-Hydroxylase levels did not change after calcitriol treatment. However, we found that higher baseline 24-hydroxylase levels and/or lower stimulation of 24-hydroxylase levels after calcitriol treatment were associated with relative resistance to calcitriol/DP006. Conclusions: The VDR represents a novel therapeutic target in poorly differentiated thyroid cancer; however, the efficacy of VDR agonist therapy to decrease viable thyroid cancer cell count cannot be predicted solely on the presence of the VDR. The FF FokI VDR genotype and high baseline 24-hydroxylase levels were associated with relative resistance to calcitriol and DP006. Therefore, identifiable markers of sensitivity or resistance to VDR agonist therapy may allow for a personalized use of these agents in poorly differentiated thyroid cancer.

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Vitamin D Receptor Polymorphisms in Differentiated Thyroid Carcinoma

Cited by 60 publications

References 36 publications

Vitamin D Receptor Gene BsmI and FokI Polymorphisms in Relation to Ovarian Cancer Risk in the Polish Population

Vitamin D Receptor Gene BsmI and FokI Polymorphisms in Relation to Ovarian Cancer Risk in the Polish Population

Low Vitamin D Status Is Not Associated With Thyroid Cancer Risk

Thyroid Cancer Resistance to Vitamin D Receptor Activation Is Associated with 24-Hydroxylase Levels But Not theffFokI Polymorphism

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