rs833061 and rs699947 on Promoter Gene of Vascular Endothelial Growth Factor (VEGF) and Associated Lung Cancer Susceptibility and Survival: A Meta-Analysis
Junwei Tu, Saibin Wang, Jianping Zhao, Jingqian Zhu, Lin Sheng, Yijun Sheng, Huijun Chen, Jianghua Tian
Department of Pneumology, Zhejiang University Jinhua Hospital, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, China (mainland)
Med Sci Monit 2014; 20:2520-2526
As 2 important SNPs located in the promoter region of VEGF gene, the roles of rs833061 (–460C>T) and rs699947 (–2578C>A) in lung cancer susceptibility and survival remain inconclusive and controversial.
Material and Methods: For better understanding of these 2 SNPs in lung cancer risk and survival, a meta-analysis was performed to pool findings of previous studies and to generate large-scale evidence.
Results: Based on the 10 eligible studies included, this study observed that the –460C>T polymorphism generally had no significant effect on lung cancer risk. However, subgroup analysis found that –460TT homozygote variant might confer significantly increased cancer risk for Asians (TT vs. CC: OR=1.69, 95% CI 1.08–2.63, p=0.02), but not in Caucasians. Similar results were observed in –2578C>A in Asians (AA vs. CC: OR=3.00, 95% CI 1.51–5.95, p=0.002; AA vs. AC: OR=3.15, 95% CI 1.00–9.91, p=0.05; AA vs. (AC+CC): OR=2.92, 95% CI 1.51–5.65, p=0.001). In lung cancer survival, 4 trials included had conflicting results. One found –460C>T polymorphism had no effect on survival, 1 observed risk increasing, while the remaining 2 observed risk decreasing. This inconsistency was closely related to the different therapeutic practices applied in different studies, the effects of which were significantly affected by VEGF expression.
Conclusions: –460TT and –2578AA homozygote might lead to significantly increased cancer risk for Asians, but the effects on survival remain to be explored. These 2 SNPs might be potential indicators of lung cancer risk for Asians and should be considered when planning chemotherapy and radiotherapy for lung cancer patients.
Keywords: Genetic Predisposition to Disease, Case-Control Studies, Lung Neoplasms - genetics, Polymorphism, Single Nucleotide - genetics, Promoter Regions, Genetic - genetics, Survival Analysis, Vascular Endothelial Growth Factor A - genetics