Fu Dian, Li Ping, Cheng Wen, Tian Feng, Xu Xiaofeng, Yi Xiaoming, Tang Chaopeng, Wang Yongzhong, Hu Quansheng, Zhang Zhengyu
Department of Urology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China.
Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Oncotarget. 2017 Apr 4;8(14):22927-22935. doi: 10.18632/oncotarget.15287.
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.
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).
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.
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.
研究血管内皮生长因子（VEGF）基因多态性中的单核苷酸多态性（SNP）、其他基因-基因及基因-吸烟相互作用与膀胱癌风险之间的关联。
VEGF基因中rs699947 - A等位基因携带者的膀胱癌风险显著高于rs699947 - CC基因型者（CA + AA与CC相比），校正比值比（95%可信区间）= 1.70（1.16 - 2.31）；VEGF基因中rs833052 - A等位基因携带者的膀胱癌风险高于rs833052 - CC基因型者（CA + AA与CC相比），校正比值比（95%可信区间）= 1.65（1.23 - 2.12）。GMDR分析表明rs2010963与吸烟之间对膀胱癌风险存在潜在相互作用。VEGF基因中rs2010963 - GC + CC基因型的当前吸烟者与VEGF基因中rs2010963 - GG基因型的从不吸烟者相比，膀胱癌风险最高，比值比（95%可信区间）= 3.25（1.71 - 4.83）。包含rs2010963 - C和rs833052 - A等位基因的单倍型与膀胱癌风险在统计学上显著增加相关，比值比（95%可信区间）= 2.21（1.12 - 3.42）。
采用广义多因素降维法（GMDR）筛选SNP与吸烟之间的最佳相互作用组合。进行逻辑回归分析以研究VEGF基因中的6个SNP以及其他基因-基因和基因-吸烟相互作用与膀胱癌风险的关联。
我们发现VEGF基因中rs699947的A等位基因、rs833052的A等位基因、rs2010963与吸烟之间的相互作用以及包含rs2010963 - C和rs833052 - A等位基因的单倍型均与膀胱癌风险增加相关。
