Association between Polymorphisms of Vitamin D Receptor and Lung Cancer Susceptibility: Evidence from an Updated Meta-analysis

Li, Meng; Liu, Xinyu; Liu, Na; Tian, Yang; Shi, Pengpeng; He, Ruiqing; Chen, Mingwei

doi:10.7150/jca.33431

Cited by 15 publications

(14 citation statements)

References 39 publications

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“…The results showed that Bsm1 and Cdx2 polymorphisms were protective factors for avoiding lung cancer incidence, while T allele and TT genotype of Taq1 were risk factors for lung cancer susceptibility. Our results were partly consistent with previous meta-analysis studies conducted by Yu et al (2018), which indicated that the Bsm1 A allele was negatively related to the lung cancer risk and the T allele carriers were at increased risk of lung cancer, and by Li et al (2019), which suggested that Bsm1, Taq1, and Cdx-2 polymorphisms may contribute to lung cancer susceptibility.…”

Section: Discussionsupporting

confidence: 92%

The Association BetweenVDRandGCPolymorphisms and Lung Cancer Risk: A Systematic Review and Meta-Analysis

Duan

Zheng

et al. 2020

Genetic Testing and Molecular Biomarkers

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Background: Lung cancer is the leading cause of cancer-related deaths worldwide, imposing an enormous economic burden on society. Several studies have identified a link between the genetic polymorphisms in vitamin D pathways and lung cancer risk; however, the results remain inconclusive. The aim of this study was to estimate the effect of polymorphisms in the vitamin D receptor (VDR) and GC genes on lung cancer risk. Methods: Eligible case-control studies published between January 2000 and December 2018 were searched and studied. The pooled odds ratio and its 95% confidence interval were used to estimate the effect. Results: Fifteen articles that included 4732 lung cancer patients and 4337 controls were identified for this study. Our results demonstrated that the VDR Bsm1 polymorphism (p < 0.05) and the TC and TT+TC genotypes of the Cdx2 polymorphism (p < 0.05) were protective factors for avoiding lung cancer incidence, while the T allele and the TT genotype of Taq1 polymorphism (p < 0.05) were risk factors for lung cancer. Ethnicity-based subgroup analyses indicated that the AA genotype of both the Apa1 and the Bsm1 polymorphisms decreased lung cancer risk in Asians, while Fok1 and Taq1 polymorphisms increased lung cancer risk in Asians. Subgroup analysis by cancer subtypes showed that certain alleles and genotypic structures of the Bsm1, Fok1, Taq1, and rs7041 were associated with nonsmall-cell lung cancer risk. Subgroup analysis by smoking status showed that the interaction between the TT genotype of Taq1 and smoking increased the risk of lung cancer. Subgroup analysis with regard to gender showed that the AA+Aa genotype of Apa1 decreased lung cancer risk in male patients. Conclusions: Our results suggest that the Bsm1 and Cdx2 polymorphisms decreased lung cancer risk, while the Taq1 polymorphism increased lung cancer risk. Moreover, the AA genotype of the Apa1 and Bsm1 variants were protective factors in Asian populations, whereas the Fok1 and Taq1 polymorphisms were risk factors for lung cancer in Asian populations. Future case-control studies with different ethnicities are still needed to generalize these associations.

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Section: Discussionsupporting

confidence: 92%

The Association BetweenVDRandGCPolymorphisms and Lung Cancer Risk: A Systematic Review and Meta-Analysis

Duan

Zheng

et al. 2020

Genetic Testing and Molecular Biomarkers

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“…Several studies have found a relationship between VDR gene polymorphisms and the risk of various cancers [30,35,46]. Also, we have previously demonstrated an association between RET gene polymorphisms and the risk of medullary thyroid cancer [18].…”

Section: Abstract Medullary Thyroid Carcinoma Vitamin D Vitamin D Receptor Polymorphism Introductionsupporting

confidence: 62%

Medullary thyroid cancer is associated with high serum vitamin D level and polymorphism of vitamin D receptors

et al. 2020

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BackgroundThyroid cancer is the most common endocrine malignancy. Studies have observed an anti-cancer effect for vitamin D and found that polymorphisms of vitamin D receptors can influence the prevalence of various cancers. The present study investigated the serum level of vitamin D and FokI, BsmI and Tru9I polymorphisms of vitamin D receptors.MethodsForty patients with medullary thyroid cancer and 40 healthy controls were investigated. The genomic DNA of the subjects was extracted using saturated salt/proteinase K and investigated by PCR sequencing. Serum levels of vitamin D were evaluated by ELISA. The results were analyzed in SPSS and GraphPad Prism 5 software.ResultsThe genotypic and allelic frequencies of FokI and BsmI polymorphisms showed no significant differences between test and control groups. For Tru9I polymorphism, Tt genotype and t allelic frequency in the test group were significantly different from those of the control group. Also, we found Tt genotype and t allelic frequency to be significantly associated with medullary thyroid cancer (MTC) type and the agressiveness of the disease. The average serum vitamin D level was 23.32 ng/mL and 18.95 ng/mL for patients and controls, respectively, and the difference between the two groups was statistically significant. Moreover, we found high serum vitamin D level to be associated with t allelic frequency.ConclusionsUnexpectedly, the mean serum vitamin D level of the test group was significantly higher than that of the control group. Tru9I polymorphism was found to be significantly correlated with the prevalence of medullary thyroid carcinoma.

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“…Previous studies have revealed that vitamin d, which can be hydroxylated to the active form 1,25(oH) 2 d3 (referred to as vitamin d or d3 in the present study), activates Vdr (9,10). Furthermore, Vdr expression is associated with cancer risk and mortality in various types of cancer, including breast, lung and colorectal cancer (11)(12)(13)(14). other studies suggested that the vitamin d and Vdr complex binds to p21 and p27 proteins, which suppress dna synthesis, inactivate mitogenic signals and inhibit tumor progression (15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 65%

Vitamin D receptor knockdown attenuates the antiproliferative, pro‑apoptotic and anti‑invasive effect of vitamin D by activating the Wnt/β‑catenin signaling pathway in papillary thyroid cancer

Pang

et al. 2020

Mol Med Rep

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Vitamin d and the vitamin d receptor (Vdr) complex have been reported to inhibit the growth of several types of tumor; however, their function in papillary thyroid cancer (PcT) remains unknown. in addition, the Wnt/β-catenin signaling pathway was discovered to serve a critical role in the pathology of PcT. Therefore, the present study aimed to determine the role of the Vdr and its association with Wnt/β-catenin signaling in vitamin d-treated PTc cells. Vdr expression was detected in human PTc cells (including Mda-T120, Mda-T85, Snu-790 and iHH4 cells) and thyroid follicular cells (nthy-ori 3-1 cells). Snu-790 and iHH4 cells were infected with Kd-Vdr or negative control (Kd-nc) lentiviruses, treated with 1,25(oH) 2 d3 (the active form of vitamin d), and subsequently referred to as the Kd-Vdr&vitd and Kd-nc&vitd groups, respectively. additionally, PTc cells infected with Kd-nc and not treated with 1,25(oH) 2 d3 were used as the normal control and referred to as the Kd-nc group. Vdr mrna and protein expression levels were increased in Mda-T120, Snu-790 and Mda-T85 cells compared to nthy-ori 3-1 cells, whereas in iHH4 cells, Vdr mrna and protein expression levels were similar to nthy-ori 3-1 cells. in Snu-790 and iHH4 cells, cell proliferation and invasion were decreased in the Kd-nc&vitd group compared with the Kd-nc group, but increased in the Kd-Vdr&vitd group compared with the Kd-nc&vitd group. cell apoptosis was increased in the Kd-nc&vitd group compared with the Kd-nc group, and decreased in the Kd-Vdr&vitd group compared with the Kd-nc&vitd group. Furthermore, the expression levels of Wnt family member 3 and catenin β1 were decreased in the Kd-nc&vitd group compared with the Kd-nc group, but increased in the Kd-Vdr&vitd group compared with the Kd-nc&vitd group. in conclusion, the present study revealed that Vdr-Kd attenuated the antiproliferative, pro-apoptotic and anti-invasive effects of vitamin d in PTc by activating the Wnt/β-catenin signaling pathway.

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Association between Polymorphisms of Vitamin D Receptor and Lung Cancer Susceptibility: Evidence from an Updated Meta-analysis

Cited by 15 publications

References 39 publications

The Association BetweenVDRandGCPolymorphisms and Lung Cancer Risk: A Systematic Review and Meta-Analysis

The Association BetweenVDRandGCPolymorphisms and Lung Cancer Risk: A Systematic Review and Meta-Analysis

Medullary thyroid cancer is associated with high serum vitamin D level and polymorphism of vitamin D receptors

Vitamin D receptor knockdown attenuates the antiproliferative, pro‑apoptotic and anti‑invasive effect of vitamin D by activating the Wnt/β‑catenin signaling pathway in papillary thyroid cancer

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