Effects of Genotype of Tumor Necrosis Factor Alpha Promoter on Bladder Tumor Grade

Jeong, Pildu; Kim, Wun Jae; Kim, Eun Jung; Kim, Jong Suk; Eum, Min Sik; Lee, Sang Cheol

Abstract

Purpose
Several polymorphic sites have been reported in the tumor necrosis factor alpha (TNF-alpha) promoter. Comparative studies on TNF-alpha production with promoter genotype have reported variable results, particularly in the 308 promoter region. Therefore, genetic polymorphism of TNF-alpha promoter region ( 308) was investigated to determine if it was associated with bladder tumor.
MATERIALS AND METHODS
The DNA from 113 and 109 respective blood samples of bladder tumor patients and controls was analyzed by a PCR-based restriction fragment length polymorphism (RFLP) method to characterize the genetic polymorphism of the 308 region of the TNF-alpha promoter. TNF-alpha expression was also checked by measuring the mRNA and protein content using a quantitative-competitive PCR and ELISA method, respectively.
RESULTS
The difference in the genetic variations of TNF-alpha promoter did not exist between the bladder tumor patients and the control group (p=0.259). The tumor grade was significantly related to the GA genotype (p=0.04). The mRNA levels of TNF-alpha in the GA genotype were significantly higher than those in the GG genotype in bladder tumors (p=0.022). The TNF-alpha serum levels in the GA genotype were significantly higher than those in the GG genotype regardless of whether there was a bladder tumor. In addition, the TNF-alpha serum levels in bladder tumor patients were significantly higher than the controls in either the GG or GA type (GG type, p=0.001; GA type, p=0.009).
CONCLUSIONS
The GA genotype of the TNF-alpha promoter region ( 308) had a significant impact on TNF-alpha production and is related to a higher-grade tumor compared to the GG genotype. The TNF-alpha serum levels in the bladder tumor patients were significantly higher than in the controls. This suggests that TNF-alpha might be involved in the tumorigenesis of the bladder.