title: Association of TP53 polymorphisms on the risk of Wilms tumor.
abstract: BACKGROUND
  Molecular factors influencing Wilms tumor (WT) development remain largely unknown. TP53 mutations seem to be restricted to the anaplastic WT subtype. However, TP53 polymorphisms do not have a defined role in the disease.
  
  
  METHODS
  To assess the impact of TP53 mutations and polymorphisms (PIN2, PIN3, and PEX4) on risk of development, age at diagnosis, and survival in WT, we analyzed 46 blood DNA samples and 31 fresh tumor DNA samples from 52 patients with WT. Sequencing of TP53 exons 2-11 was performed.
  
  
  RESULTS
  Tumor DNA analysis revealed TP53 pathogenic missense mutations (p.V197M, p.R213Q, p.R248W, and p.R337C) in four samples (12.9%). Blood DNA samples revealed a novel intronic mutation, IVS2 + 37C > T, in one patient (2.2%). Bilaterality was associated with a twofold decrease in survival (P = 0.00037). Diffuse anaplasia also presented a lower survival probability compared to patients with non-anaplastic tumors, or with focal anaplasia (P = 0.045). Patients with a TP53 somatic mutation showed survival probability of 37.5% versus 85.0% for patients with no somatic mutations, although the difference was not statistically significant (P = 0.0706). PIN3 duplicated allele was associated with a 20-month later mean age at diagnosis (P = 0.0084). TP53 PEX4 C allele showed an increased risk for WT development (P = 0.0379). No relationship was found between survival and gender, age at diagnosis, or the less frequent alleles of PIN2, PIN3, and PEX4.
  
  
  CONCLUSIONS
  Our results demonstrate an association between PIN3 and age at diagnosis, as well as an association of PEX4 and risk of development of WT.
authors.affiliation: Genetics Division, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; Department of Genetics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: R C
authors.initials: RC
authors.lastname: Andrade
authors.forename: L C A
authors.initials: LC
authors.lastname: Cardoso
authors.forename: S E
authors.initials: SE
authors.lastname: Ferman
authors.forename: P S
authors.initials: PS
authors.lastname: Faria
authors.forename: H N
authors.initials: HN
authors.lastname: Seuánez
authors.forename: M I
authors.initials: MI
authors.lastname: Achatz
authors.forename: F R
authors.initials: FR
authors.lastname: Vargas
mesh_terms: D002675:Child, Preschool; D005260:Female; D016158:Genes, p53; D005838:Genotype; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D012306:Risk; D009396:Wilms Tumor / Q000209:etiology / Q000235:genetics* / Q000401:mortality
keywords: PEX4; PIN2; PIN3; TP53; Wilms tumor