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.