Effects of Genotype of Tumor Necrosis Factor Alpha Promoter on Bladder Tumor Grade.
- Author:
Pildu JEONG
1
;
Wun Jae KIM
;
Eun Jung KIM
;
Jong Suk KIM
;
Min Sik EUM
;
Sang Cheol LEE
Author Information
1. Departments of Urology and 1Clinical Pathology, Chungbuk National University College of Medicine, Cheongju, Korea.
- Publication Type:Comparative Study ; Original Article
- Keywords:
Genetic polymorphism;
TNF-alpha;
Promoter;
Bladder tumor
- MeSH:
Carcinogenesis;
DNA;
Enzyme-Linked Immunosorbent Assay;
Genetic Variation;
Genotype*;
Humans;
Polymerase Chain Reaction;
Polymorphism, Genetic;
Polymorphism, Restriction Fragment Length;
Promoter Regions, Genetic;
RNA, Messenger;
Tumor Necrosis Factor-alpha*;
Urinary Bladder Neoplasms*;
Urinary Bladder*
- From:Korean Journal of Urology
2002;43(3):224-230
- CountryRepublic of Korea
- Language:Korean
-
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.