Importance of TP53 codon 72 and intron 3 duplication 16bp polymorphisms in prediction of susceptibility on breast cancer.
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.
Costa
Sandra
S
Life and Health Sciences Research Institute, School of Health Science, University of Minho, Braga, 4710-057, Portugal. sandracosta@ecsaude.uminho.pt
Pinto
Daniela
D
Pereira
Deolinda
D
Rodrigues
Helena
H
Cameselle-Teijeiro
Jorge
J
Medeiros
Rui
R
Schmitt
Fernando
F
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
D003062:Codon; D004273:DNA, Neoplasm