Impact of vascular endothelial growth factor gene-gene and gene-smoking interaction and haplotype combination on bladder cancer risk in Chinese population.

Aims: To investigate the association of single nucleotide polymorphisms (SNPs) within vascular endothelial growth factor (VEGF) gene polymorphisms, additional gene-gene and gene-smoking interactions with bladder cancer risk. Results: Bladder cancer risk was significantly higher in carriers of the rs699947-A allele within VEGF gene than those with rs699947-CC genotype (CA+ AA versus CC), adjusted OR (95%CI) = 1.70 (1.16-2.31), and higher in carriers of the rs833052-A allele of within VEGF gene than those with rs833052-CC genotype (CA+ AA versus CC), adjusted OR (95% CI) = 1.65 (1.23-2.12). GMDR analysis indicated a potential interaction between rs2010963 and smoking on bladder cancer risk. Current smokers with rs2010963-GC+ CC genotype within VEGF gene have the highest bladder cancer risk, compared to never smokers with rs2010963-GG genotype within VEGF gene, OR (95% CI) = 3.25 (1.71-4.83). Haplotype containing the rs2010963-C and rs833052-A alleles were associated with a statistically increased bladder cancer risk, OR (95% CI) = 2.21 (1.12-3.42). Materials and Methods: Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Logistic regression was performed to investigate association of 6 SNPs within VEGF gene, additional gene-gene and gene-smoking interaction with bladder cancer risk. Conclusions: We found that the A allele of rs699947 and the A allele of rs833052 within VEGF gene, interaction between rs2010963 and smoking, haplotype containing the rs2010963-C and rs833052-A alleles were all associated with increased bladder cancer risk.