Dataset Information

Four common vascular endothelial growth factor polymorphisms (-2578C>A, -460C>T, +936C>T, and +405G>C) in susceptibility to lung cancer: a meta-analysis.

ABSTRACT: Vascular endothelial growth factor (VEGF) is one of the key initiators and regulators of angiogenesis and it plays a vital role in the onset and development of malignancy. The association between VEGF gene polymorphisms and lung cancer risk has been extensively studied in recent years, but currently available results remain controversial or ambiguous. The aim of this meta-analysis is to investigate the associations between four common VEGF polymorphisms (i.e., -2578C>A, -460C>T, +936C>T and +405C>G) and lung cancer risk.A comprehensive search was conducted to identify all eligible studies to estimate the association between VEGF polymorphisms and lung cancer risk. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of this association.A total of 14 published case-control studies with 4,664 cases and 4,571 control subjects were identified. Our meta-analysis provides strong evidence that VEGF -2578C>A polymorphism is capable of increasing lung cancer susceptibility, especially among smokers and lung squamous cell carcinoma (SCC) patients. Additionally, for +936C>T polymorphism, increased lung cancer susceptibility was only observed among lung adenocarcinoma patients. In contrast, VEGF -460C>T polymorphism may be a protective factor among nonsmokers and SCC patients. Nevertheless, we did not find any association between +405C>G polymorphism and lung cancer risk, even when the groups were stratified by ethnicity, smoking status or histological type.This meta-analysis recommends more investigations into the relationship between -2578C>A and -460C>T lung cancer risks. More detailed and well-designed studies should be conducted to identify the causal variants and the underlying mechanisms of the possible associations.

SUBMITTER: Lin L

PROVIDER: S-EPMC3788083 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Four common vascular endothelial growth factor polymorphisms (-2578C>A, -460C>T, +936C>T, and +405G>C) in susceptibility to lung cancer: a meta-analysis.

Lin Ling L Cao Kejian K Chen Wenhu W Pan Xufeng X Zhao Heng H

PloS one 20131001 10

<h4>Background and objective</h4>Vascular endothelial growth factor (VEGF) is one of the key initiators and regulators of angiogenesis and it plays a vital role in the onset and development of malignancy. The association between VEGF gene polymorphisms and lung cancer risk has been extensively studied in recent years, but currently available results remain controversial or ambiguous. The aim of this meta-analysis is to investigate the associations between four common VEGF polymorphisms (i.e., -2 ...[more]

PMID: 24098368

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Project description:BACKGROUND: Endometriosis is regarded as a complex and heterogeneous disease in which genetic and environmental factors contribute to the phenotype. The Vascular Endothelial Growth Factor (VEGF) plays important roles in the pathogenesis of endometriosis. The present study was aimed at investigating the contribution of VEGF polymorphisms as risk factors for the development of endometriosis. This is the first study to evaluate the combined influence of the five most common VEGF polymorphisms. METHODS: This study was conducted at two hospitals from the Brazilian public health system, and comprised 294 women submitted to laparoscopic or laparotomy surgery: 182 patients had a histologically confirmed diagnosis of endometriosis (cases), whereas 112 had no evidence of the disease (controls). The VEGF polymorphisms were determined by TaqMan real-time polymerase chain reaction. The odds ratio (OR) with their 95% confidence intervals (CI) were calculated using an unconditional logistic regression model. RESULTS: Endometriosis patients and controls did not differ regarding age distribution, whereas the body mass index was significantly lower in endometriosis patients, when compared with controls (23.1?±?3.9 versus 27.3?±?5.9, P?<?0.001). The evaluation of gynecological symptoms, including dysmenorrhea, non-cyclic chronic pelvic pain, dyspareunia and infertility, indicates significantly higher prevalences among endometriosis cases. The variant allele -1154A was significantly associated with endometriosis, either considering all cases (OR: 1.90, 95% CI: 1.23-2.97), deep infiltrating endometriosis (DIE) (OR: 1.83, 95% CI: 1.16-2.90) or moderate and severe endometriosis (stages III-IV) (OR: 1.97, 95% CI: 1.21-3.19). No significant differences were found in allele or genotype distributions of the -2578C?>?A, -460 T?>?C, +405G?>?C and +936C?>?T polymorphisms between endometriosis cases and controls. A total of six haplotypes were inferred derived from four polymorphisms (-2578C?>?A, -460 T?>?C, -1154G?>?A and +405G?>?C). There was a protective association between CCGG haplotype and endometriosis, either considering all cases (OR: 0.36, 95% CI: 0.15-0.86), DIE (OR: 0.37 95% CI: 0.15 - 0.90) or stages III-IV (OR: 0.35 95% CI: 0.13 - 0.95). CONCLUSIONS: The present results indicate a positive association between VEGF -1154G?>?A and the risk of developing endometriosis, whereas the CCGG haplotype may be protective against the development of disease.

Project description:BackgroundStudies on the susceptibility of vitamin D receptor (VDR) polymorphisms to coronary artery disease (CAD) reached controversial results. We performed this study for a more accurate evaluation between the VDR polymorphisms and CAD susceptibility.MethodsPubMed, Embase, CNKI, Wan Fang, and VIP databases were searched. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to evaluate the associations. Trial sequential analysis (TSA) was introduced to estimate the positive associations. The potential functions of the VDR polymorphisms were analyzed based on the SNPinfo and ENSEMBL databases.ResultsThirteen studies were finally included. In the overall analysis, increased CAD risks were observed in the VDR rs1544410 polymorphism and verified by the TSA; for the rs2228570 and rs731236 polymorphisms, significant associations with high heterogeneity were detected; decreased risk was remarkably observed for the rs7975232 polymorphism. In the subgroup analysis, wide associations with reduced heterogeneity were observed in the rs2228570, rs1544410, and rs731236 polymorphisms. The RNAfold analysis indicated the mutant G allele of the rs1544410 polymorphism was easier to disperse from the DNA double helix structure and may have a potential crucial role in the VDR transcription process.ConclusionsOur analysis supports the role of the rs1544410 polymorphism in the VDR gene as a risk factor for CAD. The VDR rs2228570 and rs731236 polymorphisms were associated with increased CAD risks in the White population. Restrict decreased CAD risk was firstly discovered in the rs7975232 polymorphism.LimitationsFirstly, the language was restricted to English and Chinese, which will cause the limited number of studies included; secondly, other unknown polymorphisms in VDR polymorphisms could also be associated the CAD susceptibility, and more case-control studies with comprehensive clinical outcomes and GWAS studies were required; thirdly, the rs1544410, rs7975232 and rs731236 polymorphism are in strong LD, haploid factors with CAD risk need to be considered; fourthly, the mechanisms of the VDR polymorphism on the VDR gene or RNA or protein were not discussed enough, further mechanistic studies are required; at last, genetic factor was the one side for CAD susceptibility, the interaction between environmental risk factors should be considered.

Dataset Information

Four common vascular endothelial growth factor polymorphisms (-2578C>A, -460C>T, +936C>T, and +405G>C) in susceptibility to lung cancer: a meta-analysis.

Publications

Four common vascular endothelial growth factor polymorphisms (-2578C>A, -460C>T, +936C>T, and +405G>C) in susceptibility to lung cancer: a meta-analysis.

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