Frequent genotype changes at-308, and 488 regions of the tumor necrosis factor-alpha (TNF-alpha) gene in patients with prostate cancer

Purpose: Tumor necrosis factor-alpha (TNF-alpha) is involved in oncogenesis of several cancers. The purpose of this study was to investigate whether g enotype changes of TNF-alpha promoter regions (-238, -308) and at the 488 r egion are associated with human prostate cancer. Materials and Methods: The DNA from 73 cases of human prostate cancer was a nalyzed by allele-specific polymerase chain reaction to characterize the ge notype changes of three regions of the TNF-alpha gene in prostate cancer pa tients. We also determined the genotype frequency in these patients. The re lative risk of variant genotype was calculated by comparing with our previo us data from healthy controls. Results: Genetic changes were detected in 15.1% (11/73) of prostate cancer samples at 488 region of TNF-alpha. Seventy-three percent (53/73) of the pa tients showed genotype GA at -308 region of TNF-alpha. Genotype GA at 488 r egion in TNF-alpha was observed in 73% (53/73) of the cancer and 71% (52/73 ) of the normal tissue. The relative risks of incidence for prostate cancer was 14-fold higher in people with genotype GA at -308 region of TNF-alpha. The relative incidence for prostate cancer was a 17-fold higher in-patient with genotype GA at 488 region of TNF-alpha. Genotype GA at -308 of TNF-al pha was related to higher clinical tumor stage of prostate cancer than geno type G (p <0.05). Conclusions: The present study demonstrates, for the first time, that the g enotype changes in -308 and 488 regions of TNF-alpha are associated with pr ostate cancer.