title: Polymorphisms of TP53 are markers of bladder cancer vulnerability and prognosis.
abstract: OBJECTIVE
  We have reported previously that the TP53 codon72 polymorphism (rs1042522) is associated with the incidence and invasiveness of bladder cancer in a Han Chinese population. Using an enlarged sample, we investigated the role of rs1042522 and of tagSNPs that were predicted to be in linkage disequilibrium with codon72 in relation to the incidence, invasiveness, and prognosis of bladder cancer.
  
  
  METHODS
  A sample of 201 patients and 311 controls without cancer were genotyped for 5 tagSNPs using tetra-primer ARMS and/or an allele-specific PCR technique.
  
  
  RESULTS
  The genotyped data were analyzed using Haploview 4.2, and a 10,000-permutation test showed that the rs9895829G allele (P = 0.003) and the rs1788227C allele (P = 0.027) were both associated with the incidence of bladder cancer. With respect to haplotype associations, after the data were adjusted for age, the haplotypes GTT (P = 0.001) and GGTC (P < 0.001) were correlated with a low incidence of bladder cancer. In contrast, none of the TP53 haplotypes were associated significantly with high tumor grade or muscle invasiveness. On the basis of Cox regression analysis, haplotype CGCC and invasiveness were associated with cancer-related death. Structural equation modeling showed that haplotypes GGCC and CGCC played opposing roles with respect to bladder cancer-related death; haplotype GGCC was a protective factor, whereas haplotype CGCC was a risk factor.
  
  
  CONCLUSIONS
  The TP53 codon72 polymorphism appears to play a crucial role in determining the association between TP53 haplotype and the incidence and prognosis of bladder cancer. Further functional assays to confirm whether these TP53 haplotypic variants interact with the proteins N-Myc and NDRG is necessary.
authors.affiliation: Department of Urology, E-DA Hospital/I-SHOU University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hung-Yu
authors.initials: HY
authors.lastname: Lin
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Yang
authors.forename: Chun-Hsiung
authors.initials: CH
authors.lastname: Huang
authors.forename: Wen-Jen
authors.initials: WJ
authors.lastname: Wu
authors.forename: Tsan-Jung
authors.initials: TJ
authors.lastname: Yu
authors.forename: For-Wey
authors.initials: FW
authors.lastname: Lung
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D013624:Taiwan; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology
chemical_list: D016159:Tumor Suppressor Protein p53