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Background and Objective  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.    Methods  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.    Results  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.    Conclusion  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.

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Four Common Vascular Endothelial Growth Factor Polymorphisms (−2578C&gt;A, −460C&gt;T, +936C&gt;T, and +405G&gt;C) in Susceptibility to Lung Cancer: A Meta-Analysis