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

Background and ObjectiveVascular 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.MethodsA 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.ResultsA 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.ConclusionThis 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.

Vascular endothelial growth factor polymorphisms as effect modifiers of oral squamous cell carcinoma risk: A systematic review and meta-analysis

“…We could not confirm an increased OSCC risk with respect to the VEGF-promoter SNP +405 C/G, which was in accordance to the results of a previous study investigating lung cancer, which did not indicate any such association, despite stratification by ethnicity, smoking status or histological type (22).…”

“…Analysing a potential association of this SNP and the smoking behavior of the patients provided evidence of a strong interaction in patients with rheumatoid athritis for ischemic heart diseases and/or myocardial infarction (17). Lin et al (22) performed a meta-analysis on lung cancer patients among smokers. The VEGF-SNP -2578 A was associated with an increased risk of lung cancer, suggesting that this polymorphism may not be an independent risk factor.…”

“…A possible association of smoking and VEGF-SNPs with the incidence of OSCC was investigated in single studies comprising only small samples. In brief, five common VEGF-SNPs in the 5'-untranslated promoter region [-2578 C/A, -460 C/T, +405 C/G (also referred to as -634 G/C) and -1154 G/A] or the 3'-untranslated region (+936 C/T) and their association with OSCC were analysed (6,(19)(20)(21)(22). Studies investigating VEGF-SNPs and their correlation with OSCC were reviewed.…”

Relationship between vascular endothelial growth factor -2578C > a gene polymorphism and lung cancer risk: a meta-analysis

“…Lin et al . [29] included seven studies into their meta-analysis, and reported that the A allele was associated with lung cancer, but the AA and CC genotypes were not. Our metaanalysis indicated that there was an association between A allele, CC genotype and lung cancer risk in overall and Asian populations.…”

Association between +936 C>T gene polymorphism of vascular endothelial growth factor and lung cancer: A meta-analysis

“…Other meta-analysis found that there was no association between the VEGF +936C/T polymorphism and risk of gastric cancer [18], colorectal cancer [19], breast cancer [20] or lung cancer [21,22]. However, one latest meta-analysis made by Ling et al drew a partially different conclusion that +936C>T polymorphism increased lung cancer susceptibility among lung adenocarcinoma patients [23]. What's more, some published literatures have pointed that the VEGF +936C>T polymorphism may plays an uncharted role in the prognosis of lung cancer [24][25][26].…”