FREQUENT GENOTYPE CHANGES AT −308, AND 488 REGIONS OF THE TUMOR NECROSIS FACTOR - α (TNF-α) GENE IN PATIENTS WITH PROSTATE CANCER

Purpose: Tumor necrosis factor-alpha (TNF-α) is involved in oncogenesis of several cancers. The purpose of this study was to investigate whether genotype changes of TNF-α promoter regions (−238, −308) and at the 488 region are associated with human prostate cancer. Materials and Methods: The DNA from 73 cases of human prostate cancer was analyzed by allele-specific polymerase chain reaction to characterize the genotype changes of three regions of the TNF-α gene in prostate cancer patients. We also determined the genotype frequency in these patients. The relative risk of variant genotype was calculated by comparing with our previous data from healthy controls. Results: Genetic changes were detected in 15.1% (11/73) of prostate cancer samples at 488 region of TNF-α. Seventy-three percent (53/73) of the patients showed genotype GA at −308 region of TNF-α. Genotype GA at 488 region in TNF-α 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 was14-fold higher in people with genotype GA at −308 region of TNF-α. The relative incidence for prostate cancer was a 17-fold higher in-patient with genotype GA at 488 region of TNF-α. Genotype GA at −308 of TNF-α was related to higher clinical tumor stage of prostate cancer than genotype G (p Conclusions: The present study demonstrates, for the first time, that the genotype changes in −308 and 488 regions of TNF-α are associated with prostate cancer.