title: The intronic G13964C variant in p53 is not a high-risk mutation in familial breast cancer in Australia.
abstract: BACKGROUND
  Mutations in BRCA1 and BRCA2 account for approximately 50% of breast cancer families with more than four affected cases, whereas exonic mutations in p53, PTEN, CHK2 and ATM may account for a very small proportion. It was recently reported that an intronic variant of p53--G13964C--occurred in three out of 42 (7.1%) 'hereditary' breast cancer patients, but not in any of 171 'sporadic' breast cancer control individuals (P = 0.0003). If this relatively frequent occurrence of G13964C in familial breast cancer and absence in control individuals were confirmed, then this would suggest that the G13964C variant plays a role in breast cancer susceptibility.
  
  
  METHODS
  We genotyped 71 familial breast cancer patients and 143 control individuals for the G13964C variant using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis.
  
  
  RESULTS
  Three (4.2%; 95% confidence interval [CI] 0-8.9%) G13964C heterozygotes were identified. The variant was also identified in 5 out of 143 (3.5%; 95% CI 0.6-6.4%) control individuals without breast cancer or a family history of breast cancer, however, which is no different to the proportion found in familial cases (P = 0.9).
  
  
  CONCLUSIONS
  The present study would have had 80% power to detect an odds ratio of 4.4, and we therefore conclude that the G13946C polymorphism is not a 'high-risk' mutation for familial breast cancer.
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Marsh
authors.forename: A B
authors.initials: AB
authors.lastname: Spurdle
authors.forename: B C
authors.initials: BC
authors.lastname: Turner
authors.forename: S
authors.initials: S
authors.lastname: Fereday
authors.forename: H
authors.initials: H
authors.lastname: Thorne
authors.forename: G M
authors.initials: GM
authors.lastname: Pupo
authors.forename: G J
authors.initials: GJ
authors.lastname: Mann
authors.forename: J L
authors.initials: JL
authors.lastname: Hopper
authors.forename: J F
authors.initials: JF
authors.lastname: Sambrook
authors.forename: G
authors.initials: G
authors.lastname: Chenevix-Trench
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D017931:DNA Primers