Vitamin D and Lung Cancer

Shaurova, Tatiana; Seshadri, Mukund; Hershberger, Pamela A.

doi:10.1016/b978-0-12-809963-6.00101-2

Cited by 5 publications

(6 citation statements)

References 148 publications

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“…Vitamin D may play a beneficial role in pulmonary inflammation and may control lung cancer by favorably altering the lung tumor microenvironment and immune function (Prietl et al, 2013). Evidences have suggested that vitamin D metabolites exhibit chemopreventive, antiproliferative, and antimetastatic activity in preclinical models of lung cancer (Shaurova et al, 2018). Variations in vitamin D may influence the status of vitamin D and its functions, in turn, affecting disease progression.…”

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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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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“…Vitamin D has been attributed a favorable role in pulmonary inflammation, and its alteration was thought to be linked to lung cancer progression by modulating the tumor microenvironment and immune function ( Prietl et al, 2013 ). Furthermore, vitamin D metabolites have been found to possess anticancer potency in preclinical models of lung cancer ( Shaurova et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Revealing the association between vitamin D metabolic pathway gene variants and lung cancer risk: a systematic review and meta-analysis

Elsalahaty,

Alkafaas,

Bashir

et al. 2024

Front. Genet.

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Lung cancer is a crucial global issue, with more than one million deaths annually. While smoking is considered the main etiology of the disease, several genetic variants are associated with it. Alterations in vitamin D pathway genes have also been studied in regards to lung cancer, but the findings have been inconclusive. We here present a systematic review and meta-analysis of seven genes in this pathway: CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP3A5, GC, and VDR. Four databases (PubMed, Scopus, Cochrane Library, and Web of Science (WOS) databases) were searched. From these, 16 eligible case–control studies comprising 6,206 lung cancer cases and 7,272 health controls were obtained. These studies were subjected to comprehensive data extraction and quality scoring, and the pooled odds ratio with a 95% confidence interval was calculated to estimate the effect of each variant along with heterogeneity analysis and a risk of bias assessment. Our meta-analysis revealed an association between CYP3A4 (rs2740574) and lung cancer in the allelic, heterozygous, and dominant models. In addition, both VDR (Fok1: rs2228570) and VDR (Cdx-2: rs11568820) displayed a protective role in lung cancer development in the heterozygous and dominant models. Furthermore, VDR (Taq1: rs731236) showed a decreased risk of lung cancer in the allelic, homozygous, and recessive models. Similarly, VDR (BsmI: rs1544410) had a positive effect on lung cancer risk when subjected to allelic and recessive models. Our meta-analysis revealed the lack of association of CYP2R1 (rs10741657), CYP27B1 (rs3782130), CYP27B1 (rs10877012), CYP24A1 (rs6068816), CYP24A1 (rs4809960), CYP3A5 (rs776746), GC (rs7041), GC (rs4588), and VDR (ApaI: rs7975232) with lung cancer. Our work revealed that CYP3A4 (rs2740574) can represent an independent risk factor for lung cancer. This conclusion can aid better personalized medicine for lung cancer management, while further assessment for genetic variants of CYP3A4, CYP27B1, CYP24A1, GC, and VDR is still required to address more robust evidence.

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“…It has been reported that the role of HDAC in LUAD is closely related to EZH2. NSCLC patients with high expression of HDAC and EZH2 have a low survival rate (Shi et al, 2019), and EGFR and PI3K are classic regulatory pathways involved in the development of LUAD (Wei et al, 2019;Shaurova et al, 2020). This motivates further exploration and clinical application of these potential targets.…”

Section: Discussionmentioning

confidence: 99%

Catenin Alpha-2 Mutation Changes the Immune Microenvironment in Lung Adenocarcinoma Patients Receiving Immune Checkpoint Inhibitors

et al. 2021

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Background: Lung cancer has always been the most prevalent cancer. Lung adenocarcinoma (LUAD) is the most common lung cancer subtype and has a high tumor mutation rate. In addition to KRAS, EGFR, ALK, HER2, ROS1, and BRAF, which are known to have high mutation rates, we discovered some new mutated genes, such as catenin alpha-2 (CTNNA2), in LUAD patients treated with immune checkpoint inhibitors (ICIs). These mutant genes are potential therapeutic targets for LUAD.Methods: We analyzed a cohort of LUAD patients with somatic mutation and survival data in the Cancer Genome Atlas (TCGA) database and a cohort of LUAD patients receiving immune checkpoint inhibitors with clinical data and whole-exome sequencing (WES) mutation data to evaluate the role of CTNNA2 gene mutation in LUAD. In addition, CIBERSORT was used to analyze the immune characteristics of CTNNA2 wild-type patients and CTNNA2 mutant-type patients, and gene set enrichment analysis (GSEA) was employed for pathway enrichment analysis. The results were verified by downloading data regarding the drug sensitivity of LUAD cell lines from the Genomics of Drug Sensitivity in Cancer (GDSC) database.Results: We found that CTNNA2 mutation was associated with longer overall survival (OS) in LUAD patients. Analysis of the cohort from the Cancer Genome Atlas showed that patients with CTNNA2 mutation had more tumor neoantigens and a greater tumor mutation burden (TMB). Through further analysis of the tumor immune microenvironment, we found that in LUAD patients with CTNNA2 mutations, the gene expression levels of chemokine C-X-C motif chemokine 9 (CXCL9) and granzyme B (GZMB) were elevated, and the gene expression level of inhibitory receptor killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) was significantly reduced. These alterations might affect gene expression in macrophages, NK cells, and mast cell markers. In addition, LUAD patients with CTNNA2 mutation had a significantly increased number of mutations in DNA damage response (DDR) genes. The drug susceptibility results and gene set enrichment analysis showed that after CTNNA2 mutation occurred, changes were found in the DNA damage response pathway, the phosphoinositide 3-kinase (PI3K) pathway and others, indicating that CTNNA2 mutation can regulate the activation of PI3K and DDR pathways.Conclusion: Our findings provide novel insights into the underlying pathogenesis of LUAD. CTNNA2 mutation can change the immune microenvironment, thereby improving patient prognosis. The results also suggest that CTNNA2 may become a new biomarker and therapeutic target for LUAD in the future.

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Vitamin D and Lung Cancer

Cited by 5 publications

References 148 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

Revealing the association between vitamin D metabolic pathway gene variants and lung cancer risk: a systematic review and meta-analysis

Catenin Alpha-2 Mutation Changes the Immune Microenvironment in Lung Adenocarcinoma Patients Receiving Immune Checkpoint Inhibitors

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