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

Dian Fu,Ping Li,Feng Tian,Zhengyu Zhang,Chaopeng Tang,Wen Cheng,Xiaofeng Xu,Xiaoming Yi,Quansheng Hu,Yongzhong Wang

doi:10.18632/oncotarget.15287

Abstract

AimsTo 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.ResultsBladder 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 MethodsGeneralized 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.ConclusionsWe 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.

Highlights

As we all known that bladder cancer was an important health problem, and was the 7th and 17th most frequent cancer in males and females, respectively [1], and in China, the occurrence of bladder cancer has dramatically increased from 1991 to 2009, and it accounted for more than 20,000 deaths in China in 2009 [2, 3]
Bladder cancer risk was significantly higher in carriers of the rs699947A allele within vascular endothelial growth factor (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)
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

Summary

Introduction

As we all known that bladder cancer was an important health problem, and was the 7th and 17th most frequent cancer in males and females, respectively [1], and in China, the occurrence of bladder cancer has dramatically increased from 1991 to 2009, and it accounted for more than 20,000 deaths in China in 2009 [2, 3]. Many single-nucleotide polymorphisms (SNPs) of VEGF have been reported [7, 8], and some SNPs have been reported association with susceptibility to several types of tumors, including renal and gastric cancers [9, 10]. Some studies focused on the association between VEGF gene polymorphisms and bladder cancer risks were conducted, but these studies concluded inconsistent results. Several large cohort studies in Europe and the USA have demonstrated that cigarette smoking was an important risk factor for bladder cancer [11, 12], and several genes have been reported interaction with smoking on bladder cancer susceptibility, such as XPC-PAT gene [13], no study focused on impact of interaction between VEGF gene and smoking on bladder cancer risk. The present study aimed to evaluate the influence of VEGF SNPs, possible gene- gene, genesmoking interaction and haplotype combinations on bladder cancer risk base on a Chinese population

Methods

Results

Conclusion