title: Importance of TP53 codon 72 and intron 3 duplication 16bp polymorphisms in prediction of susceptibility on breast cancer.
abstract: BACKGROUND
  TP53 is one of major tumour suppressor genes being essential in preservation of genome integrity. Two very common polymorphisms have been demonstrated to contribute to cancer susceptibility and tumour behaviour. The purpose of this study was to evaluate the role of Arg72Pro and PIN3 Ins16bp polymorphisms in TP53 gene as genetic susceptibility and predictive markers to breast cancer.
  
  
  METHODS
  We analysed DNA samples from 264 breast cancer patients and 440 controls, for TP53 Arg72Pro and PIN3 Ins16bp polymorphisms using PCR-RFLP.
  
  
  RESULTS
  We observed that women with A2A2 genotype have increased risk for developing breast cancer, either in women with or without familial history (FH) of the disease (OR = 4.40, 95% CI 1.60-12.0; p = 0.004; OR = 3.88, 95% CI 1.18-12.8; p = 0.026, respectively). In haplotype analysis, statistically significant differences were found between TP53 Arg-A2 haplotype frequencies and familial breast cancer cases and the respective control group (OR = 2.10, 95% CI 1.08-4.06; p = 0.028). Furthermore, both TP53 polymorphisms are associated with higher incidence of lymph node metastases.
  
  
  CONCLUSIONS
  Our findings suggest TP53 PIN3 Ins16bp polymorphism as a real risk modifier in breast cancer disease, either in sporadic and familial breast cancer. Furthermore, both TP53 polymorphisms are associated with higher incidence of lymph node metastases.
authors.affiliation: Life and Health Sciences Research Institute, School of Health Science, University of Minho, Braga, 4710-057, Portugal. sandracosta@ecsaude.uminho.pt
authors.forename: Sandra
authors.initials: S
authors.lastname: Costa
authors.forename: Daniela
authors.initials: D
authors.lastname: Pinto
authors.forename: Deolinda
authors.initials: D
authors.lastname: Pereira
authors.forename: Helena
authors.initials: H
authors.lastname: Rodrigues
authors.forename: Jorge
authors.initials: J
authors.lastname: Cameselle-Teijeiro
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
authors.forename: Fernando
authors.initials: F
authors.lastname: Schmitt
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D003062:Codon; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D003062:Codon; D004273:DNA, Neoplasm