Association of bladder tumors and GA genotype of -308 nucleotide in tumor necrosis factor-alpha promoter with greater tumor necrosis factor-alpha expression.
OBJECTIVE
To investigate whether the genetic polymorphism of the -308 nucleotide in the tumor necrosis factor-alpha (TNF-alpha) promoter is associated with bladder cancer.


METHODS
DNA samples from blood and tumor were analyzed by polymerase chain reaction-based restriction fragment length polymorphism to characterize the genetic polymorphism of the -308 nucleotide in the TNF-alpha promoter. TNF-alpha mRNA expression levels were assessed by quantitative competitive polymerase chain reaction, and the serum concentrations of TNF-alpha were measured using enzyme-linked immunosorbent assay.


RESULTS
Patients with bladder tumor and control subjects did not differ in their genetic polymorphism of the -308 nucleotide (P = 0.259). However, the relation of the tumor grade with the GA phenotype was statistically significant (P = 0.04). TNF-alpha mRNA concentrations were also significantly greater in the GA genotype than in the GG genotype (P = 0.022). The TNF-alpha serum levels of the GA genotype were significantly greater than those of the GG genotype for both patients and controls. However, patients with bladder tumor had significantly greater TNF-alpha serum levels than did the controls for both the GG and the GA genotypes (GG type, P = 0.001; GA type, P = 0.009).


CONCLUSIONS
The genotype of the -308 nucleotide in the TNF-alpha promoter had a statistically significant effect on TNF-alpha production and was related to the bladder tumor grade. The GA polymorphism might be associated with a statistically significant increase in gene transcription. That the TNF-alpha serum levels were greater in the patients with bladder tumor compared with controls suggests that high TNF-alpha production is associated with bladder tumor development and that bladder tumors may secrete TNF-alpha.
Jeong
Pildu
P
Department of Urology, Chungbuk National University College of Medicine and Institute for Tumor Research, Cheongju, Korea.
Kim
Eun-Jung
EJ
Kim
Eung-Gook
EG
Byun
Seok-Soo
SS
Kim
Choung Soo
CS
Kim
Wun-Jae
WJ
D005838:Genotype; D006801:Humans; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha