Vitamin D Receptor Genetic Variants are Associated With Chemotherapy Response and Prognosis in Patients With Advanced Non–Small-Cell Lung Cancer

Xiong, Liwen; Cheng, Jinsong; Gao, Jinyu; Wang, Jipeng; Liu, Xiaoning; Wang, Lixin

doi:10.1016/j.cllc.2013.01.004

Cited by 18 publications

(27 citation statements)

References 28 publications

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“…An increased risk comparing TT vs. CC in Taq1 in our study is consistent with the results observed in previous studies [50,51,52]. On the other hand, there are a few other studies that have also found no association with increased risk [53,54]. A decreased NSCLC risk with Bsm1 in our findings is consistent with the study of Heist et al [55].…”

Section: Discussionsupporting

confidence: 93%

“…Medical history, history of pulmonary disease, family history of lung cancer as well as other lifestyle behaviors were also considered. Exclusion criteria included symptomatic brain metastases, spinal cord compression, uncontrolled massive pleural effusion, and other chronic diseases including history of pulmonary disease, and preoperative radiotherapy or chemotherapy [53,73]. Subjects taking calcium and vitamin D supplements during the previous 6 months were also excluded from the study.…”

Section: Methodsmentioning

confidence: 99%

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Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk

Cheng

Yang

2016

IJMS

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Epidemiological studies regarding the relationship between vitamin D, genetic polymorphisms in the vitamin D metabolism, cigarette smoke and non-small cell lung cancer (NSCLC) risk have not been investigated comprehensively. To search for additional evidence, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and radioimmunoassay method were utilized to evaluate 5 single-nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR), 6 SNPs in 24-hydroxylase (CYP24A1), 2 SNPs in 1α-hydroxylase (CYP27B1) and 2 SNPs in vitamin D-binding protein (group-specific component, GC) and plasma vitamin D levels in 426 NSCLC cases and 445 controls from China. Exposure to cigarette smoke was ascertained through questionnaire information. Multivariable linear regressions and mixed effects models were used in statistical analysis. The results showed that Reference SNP rs6068816 in CYP24A1, rs1544410 and rs731236 in VDR and rs7041 in GC were statistically significant in relation to reduction in NSCLC risk (p < 0.001–0.05). No significant connection was seen between NSCLC risk and overall plasma 25-hydroxyvitamin D [25(OH)D] concentrations, regardless of smoking status. However, the mutation genotype of CYP24A1 rs6068816 and VDR rs1544410 were also significantly associated with increased 25(OH)D levels only in both the smoker and non-smoker cases (p < 0.01–0.05). Meanwhile, smokers and non-smokers with mutated homozygous rs2181874 in CYP24A1 had significantly increased NSCLC risk (odds ratio (OR) = 2.14, 95% confidence interval (CI) 1.47–3.43; p = 0.031; OR = 3.57, 95% CI 2.66–4.74; p = 0.019, respectively). Smokers with mutated homozygous rs10735810 in VDR had significantly increased NSCLC risk (OR = 1.93, 95% CI 1.41–2.76; p = 0.015). However, smokers with mutated homozygous rs6068816 in CYP24A1 had significantly decreased NSCLC risk (OR = 0.43, 95% CI 0.27–1.02; p = 0.006); and smokers and non-smokers with mutated homozygous rs1544410 in VDR had significantly decreased NSCLC risk (OR = 0.51, 95% CI 0.34–1.17; p = 0.002; OR = 0.26, 95% CI 0.20–0.69; p = 0.001, respectively). There are significant joint effects between smoking and CYP24A1 rs2181874, CYP24A1 rs6068816, VDR rs10735810, and VDR rs1544410 (p < 0.01–0.05). Smokers with mutated homozygous rs10735810 in VDR had significantly increased NSCLC risk (OR = 1.93, 95% CI 1.41–2.76; p = 0.015). In summary, the results suggested that the lower the distribution of vitamin D concentration, the more the genetic variations in CYP24A1, VDR and GC genes may be associated with NSCLC risk. In addition, there are significant joint associations of cigarette smoking and vitamin D deficiency on NSCLC risk.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk

Cheng

Yang

2016

IJMS

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“…Heist et al (2008) showed that the T allele of the VDR Fok1 polymorphism and the G-T-C (Cdx-2-Fok1-Bsm1) haplotype were associated with worse survival of NSCLC. An effect of Apa1 polymorphisms of the VDR gene on the chemotherapy response in patients with NSCLC has also been identified, as well as a prognostic role of the VDR gene polymorphisms in Chinese patients with advanced NSCLC (Xiong et al, 2013). GC has immunomodulatory functions in lung, predominantly relating to macrophage activation and neutrophil chemotaxis (Chun, 2012).…”

Section: Discussionmentioning

confidence: 99%

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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“…Apart from the classical actions on calcium homeostasis and bone mineralization, vitamin D has an increasingly recognized array of antiinflammatory, immunomodulatory, antiproliferative, and antiangiogenic properties. Serum vitamin D and/or genetic variants of its receptor have been associated with the incidence, 5,6 pathogenesis, 7 histological differentiation, 8 angiogenetic and metastatic potential, 9 response to chemotherapy 10 and overall survival 11 in both early 12,13 and advanced stage 14 lung cancer -the commonest cause of malignant pleural disease. 4 Although the design of those studies does not allow for proof of causality, further evidence implicates vitamin D in malignancy.…”

Section: Introductionmentioning

confidence: 99%

“…4 Although the design of those studies does not allow for proof of causality, further evidence implicates vitamin D in malignancy. Serum vitamin D and/or genetic variants of its receptor have been associated with the incidence, 5,6 pathogenesis, 7 histological differentiation, 8 angiogenetic and metastatic potential, 9 response to chemotherapy 10 and overall survival 11 in both early 12,13 and advanced stage 14 lung cancer -the commonest cause of malignant pleural disease. At a molecular level, vitamin D has been shown to modulate the expression of adhesion proteins such as E-cadherin and b-catenin 15,16 whose reduced expression is associated with tumor cell dedifferentiation, local invasion, regional metastasis, and reduced survival in non-small cell lung cancer.…”

Section: Introductionmentioning

confidence: 99%

25‐hydroxyvitamin D in malignant pleural disease: a prospective cohort study

Panagiotou

Papaioannou

Κostikas

et al. 2016

Clinical Respiratory J

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Vitamin D Receptor Genetic Variants are Associated With Chemotherapy Response and Prognosis in Patients With Advanced Non–Small-Cell Lung Cancer

Cited by 18 publications

References 28 publications

Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk

Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk

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

25‐hydroxyvitamin D in malignant pleural disease: a prospective cohort study

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