Association of bladder tumors and GA genotype of-308 nucleotide in tumor necrosis factor-alpha promoter with greater tumor necrosis factor-alpha expression

Objectives. 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. (C) 2004 Elsevier Inc.