title: Tumor necrosis factor-alpha gene mutations and genotype changes in renal cell carcinoma.
abstract: OBJECTIVE
  We tested the hypothesis that genotype changes in the promoter region of tumor necrosis factor-alpha and exon 1 are associated with renal cell carcinoma.
  
  
  METHODS
  We analyzed genotypic changes at the 3 polymorphic loci of tumor necrosis factor-alpha -238, -308 and 488 using tumor and normal tissues from 81 Japanese patients with renal cell carcinoma.
  
  
  RESULTS
  Of the 81 patients 14 (17%) had point mutations from G to A, including 8 (57%) with point mutations at multiple loci. Six of the 8 patients (75%) with point mutations at multiple loci were classified with stage 4 renal cell carcinoma. Of the 81 patients 14 were classified with stage 4 carcinoma, including 9 (64%) with point mutation from G to A. Normal tissue from cancer patients showed an increased frequency of the GA genotype at loci -238 and 488 compared to healthy controls (37% versus 9% and 30% versus 12%, respectively). The relative risk of renal cell carcinoma was 6.5-fold higher in patients with the GA genotype at locus -238 (p <0.001) and 2.9-fold higher in those with the GA genotype at locus 488 (0.01 < p <0.025) when comparing normal tissue from renal cell carcinoma patients with that of healthy controls.
  
  
  CONCLUSIONS
  Point mutation from G to A, and the GA genotype at loci -238 and 488 of the TNF-alpha gene were common in patients with advanced renal cell carcinoma. The genotype change at loci -238 and 488 of the TNF-alpha gene are associated with renal cancer pathogenesis.
authors.affiliation: Department of Urology, Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, USA.
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: M
authors.initials: M
authors.lastname: Sasaki
authors.forename: D
authors.initials: D
authors.lastname: Nojima
authors.forename: B R
authors.initials: BR
authors.lastname: Oh
authors.forename: N
authors.initials: N
authors.lastname: Ishii
authors.forename: K
authors.initials: K
authors.lastname: Miura
authors.forename: R
authors.initials: R
authors.lastname: Dahiya
mesh_terms: D000328:Adult; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D009154:Mutation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha