Research Papers:

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, Wen Cheng, Feng Tian _, Xiaofeng Xu, Xiaoming Yi, Chaopeng Tang, Yongzhong Wang, Quansheng Hu and Zhengyu Zhang

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Oncotarget. 2017; 8:22927-22935. https://doi.org/10.18632/oncotarget.15287

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Dian Fu1,*, Ping Li1,*, Wen Cheng1, Feng Tian2, Xiaofeng Xu1, Xiaoming Yi1, Chaopeng Tang1, Yongzhong Wang3, Quansheng Hu4, Zhengyu Zhang1

1Department of Urology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China

2Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China

3Department of Urology, The First People’s Hospital of Huoqiu City, Huoqiu, Anhui, China

4Department of Urology, Southwest Hospital of the Third Military Medical University, Chongqing, China

*These authors contributed equally to this work

Correspondence to:

Xiaoming Yi, email: [email protected]

Chaopeng Tang, email: [email protected]

Feng Tian, email: [email protected]

Keywords: bladder cancer, vascular endothelial growth factor, single nucleotide polymorphisms, interaction, smoking

Received: December 08, 2016     Accepted: January 27, 2017     Published: February 11, 2017


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.

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