Abstract

BACKGROUND: 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