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

Abstract

ObjectivesTo investigate whether the genetic polymorphism of the −308 nucleotide in the tumor necrosis factor-alpha (TNF-α) promoter is associated with bladder cancer. MethodsDNA 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-α promoter. TNF-α mRNA expression levels were assessed by quantitative competitive polymerase chain reaction, and the serum concentrations of TNF-α were measured using enzyme-linked immunosorbent assay. ResultsPatients 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-α mRNA concentrations were also significantly greater in the GA genotype than in the GG genotype (P = 0.022). The TNF-α 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-α serum levels than did the controls for both the GG and the GA genotypes (GG type, P = 0.001; GA type, P = 0.009). ConclusionsThe genotype of the −308 nucleotide in the TNF-α promoter had a statistically significant effect on TNF-α 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-α serum levels were greater in the patients with bladder tumor compared with controls suggests that high TNF-α production is associated with bladder tumor development and that bladder tumors may secrete TNF-α.