title: Association of polymorphisms in TGFB1 and prostate cancer prognosis.
abstract: OBJECTIVE
  Because of the role of TGFB1 in prostate cancer and progression, we hypothesized that polymorphisms of TGFB1 at C-509T may be associated with prostate cancer risk and/or more aggressive tumors.
  
  
  METHODS
  This is a case-control study. Controls consisted of male volunteers 40 years old or older with a normal digital rectal examination and prostate specific antigen 2.5 ng/ml or less. Cases consisted of men with biopsy proven prostate cancer. High grade prostate cancer included all cancers of Gleason sum 7 or greater. Poor prognosis in cases was defined as any stage with Gleason sum 8-10, pT3A (if Gleason sum was greater than 7), pT3B or higher (all Gleason sums), any N1 or higher, any M1 or higher, or any documented PSA recurrence (biochemical failure). Single nucleotide polymorphisms were genotyped using allelic discrimination assays. Logistic regression models were used to estimate the OR with the corresponding 95% CI for individual racial/ethnic groups. Allelic frequency across ethnic/racial groups was compared using Pearson's chi-square test.
  
  
  RESULTS
  A total of 653 cases and 1,476 controls were genotyped at C-509T. The TT genotype showed a significant protective effect against high grade prostate cancer (OR 0.482, 95% CI 0.274-0.849). In addition, the TT genotype was associated with a decreased risk of poor prognosis prostate cancer (OR 0.488, 95% CI 0.236-1.009). Limiting analysis to nonHispanic white men showed that the TT genotype had an even more pronounced protective effect for poor prognosis prostate cancer (OR 0.297, 95% CI 0.100-0.887). Finally, there was a significant difference in the distribution of allelic frequency across racial/ethnic groups (p <0.0001).
  
  
  CONCLUSIONS
  We observed an association between single nucleotide polymorphisms of TGFB1 at C-509T and a decreased risk of aggressive prostate cancer. The TT genotype of TGFB1 at C-509T demonstrates a protective effect against high grade prostate cancer and cases with poor prognosis.
authors: Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors: Timothy C
authors: TC
authors: Brand
authors: Carlos
authors: C
authors: Bermejo
authors: Edith
authors: E
authors: Canby-Hagino
authors: Dean A
authors: DA
authors: Troyer
authors: Jacques
authors: J
authors: Baillargeon
authors: Ian M
authors: IM
authors: Thompson
authors: Robin J
authors: RJ
authors: Leach
authors: Susan L
authors: SL
authors: Naylor
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D005006:Ethnicity / Q000235:genetics*; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1