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.
Highlights
Lung cancer, characterized by uncontrolled cell growth in tissues of the lung [1], accounts for 13% (1.6 million) of the total cancer cases and 18% (1.4 million) of total deaths in 2008 [2]
Inclusion and Exclusion Criteria Our meta-analysis included genetic association studies fulfilling the following inclusion criteria: (a) a case-control, cohort or crosssectional study must evaluated at least one of four polymorphisms of Vascular endothelial growth factor (VEGF) gene and lung cancer risk; (b) the diagnosis of lung cancer patients was confirmed pathologically and controls were confirmed as cancer-free patients; (c) inclusion of sufficient data on the size of the sample, odds ratio (OR), and 95% confidence interval (CI) and (d) articles were published in the English or Chinese language
All included studies extracted DNA from peripheral blood and the VEGF polymorphisms were determined by classic polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 12 studies, by TaqMan in 1 study, and by primer-introduced restriction analysis (PIRA)-PCR in another study
Summary
Lung cancer, characterized by uncontrolled cell growth in tissues of the lung [1], accounts for 13% (1.6 million) of the total cancer cases and 18% (1.4 million) of total deaths in 2008 [2]. Vascular endothelial growth factor (VEGF), known as vascular permeability factor, is one of the key initiators and regulators of angiogenesis and it plays a critical role in the progress and prognosis of malignancy [8,9,10]. 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., 22578C.A, 2460C.T, +936C.T and +405C.G) and lung cancer risk
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