title: The p53 Arg72Pro and Ins16bp polymorphisms and their haplotypes are not associated with breast cancer risk in BRCA-mutation negative familial cases.
abstract: BACKGROUND
  Germline disease-causing mutations in BRCA1 and BRCA2 genes confer high risk of breast and ovarian cancer, but account approximately for only 15% of familial cases. Theoretical models and experimental observations have indicated that the remaining familial aggregations would be explained by low-penetrance alleles. Moreover, alleles acting as genetic modifiers would modulate the breast cancer risk in carriers of BRCA mutations. The Ins16bp and Arg72Pro polymorphisms of p53 were implicated in breast cancer and recently it has been shown that these polymorphisms could have an effect when combined as specific haplotypes. Here, we investigated the possible role of the Ins16bp and Arg72Pro polymorphisms and their haplotypes as low-penetrance alleles in familial breast cancer.
  
  
  METHODS
  The Ins16bp and Arg72Pro polymorphisms were genotyped in a total of 350 familial index cases affected with breast cancer and negative for mutations in BRCA genes, and 352 controls. The Ins16bp and Arg72Pro polymorphisms were studied separately, and as haplotypes and haplotypes combinations.
  
  
  RESULTS
  None of the performed analyses resulted statistically significant.
  
  
  CONCLUSIONS
  These observations suggested that neither the Ins16bp or Arg72Pro polymorphisms considered separately, nor any related haplotype, were associated with breast cancer risk in BRCA-mutation negative familial cases.
authors.affiliation: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Vecchi
authors.forename: Paolo
authors.initials: P
authors.lastname: Verderio
authors.forename: Sara
authors.initials: S
authors.lastname: Pizzamiglio
authors.forename: Siranoush
authors.initials: S
authors.lastname: Manoukian
authors.forename: Loris
authors.initials: L
authors.lastname: Bernard
authors.forename: Valeria
authors.initials: V
authors.lastname: Pensotti
authors.forename: Sara
authors.initials: S
authors.lastname: Volorio
authors.forename: Fernando
authors.initials: F
authors.lastname: Ravagnani
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
authors.forename: Paolo
authors.initials: P
authors.lastname: Peterlongo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53