Impact of Vascular Endothelial Growth Factor Gene Polymorphisms and Their Interactions with Environmental Factors on Susceptibility to Renal Cell Carcinoma

Abstract

Aims: This study aimed to investigate the association of single nucleotide polymorphisms (SNPs) within vascular endothelial growth factor (VEGF) gene and additional gene-environment interaction with renal cell carcinoma (RCC) risk. Methods: PCR-restriction fragment length polymorphism was performed to detect SNPs. Hardy-Weinberg equilibrium and allele frequencies in cases and controls were calculated using SNPStats (http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among 4 SNPs, smoking, and alcohol drinking. Logistic regression was performed to investigate the association between 4 SNPs within VEGF gene, additional gene-smoking interaction, and RCC risk. Results: RCC risk was significantly higher in carriers with the T allele of rs833061 within VEGF gene than those with CC genotype (CT+TT vs. CC) {adjusted odds ratio (OR) (95% confidence interval [CI]) = 1.71 (1.17-2.32), p = 0.002} and higher in carriers with the A allele of rs699947 within VEGF gene than those with GG genotype (GA+AA vs. GG) (adjusted OR [95% CI] = 1.64 [1.27-2.10], p < 0.001). GMDR analysis indicated a significant 2-locus model (p = 0.0010) involving rs833061 and smoking. The cross-validation consistency of the 2-locus model was 10/10, and the testing accuracy was 60.72%. Current smokers with rs833061-CT+TT genotype had the highest RCC risk, compared to never smokers with rs833061-CC genotype within VEGF gene (OR [95% CI] = 3.02 [1.84-4.23], p < 0.001). Conclusions: We found that the T allele of rs833061 and the A allele of rs699947 within VEGF gene, and the interaction between rs833061 and smoking were all associated with increased RCC risk.

The relationship between VEGF-460(T>C) polymorphism and cancer risk: A systematic review and meta-analysis based on 46 reports

“…54 studies comprising 60 reports were enrolled initially, published literature [19–68] and gray literature. [69–72] We included 46 English-language articles and 8 Chinese-language articles.…”

“…Numerous institutions have performed extensive studies to demonstrate the relationship between SNPs in VEGF and cancer, especially for VEGF-460(T/C). [19–78] However, different and even contradictory results were obtained. Several investigators have conducted meta-analyses to evaluate this link comprehensively.…”