Importance of TP53 codon 72 and intron 3 duplication 16bppolymorphisms in prediction of susceptibility on breast cancer

Sandra Costa,Daniela Pinto,Fernando Schmitt,Deolinda Pereira,Jorge Cameselle-Teijeiro,Helena Rodrigues,Rui Medeiros

doi:10.1186/1471-2407-8-32

Abstract

BackgroundTP53 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.MethodsWe analysed DNA samples from 264 breast cancer patients and 440 controls, for TP53 Arg72Pro and PIN3 Ins16bp polymorphisms using PCR-RFLP.ResultsWe 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.ConclusionOur 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.

Highlights

TP53 is one of major tumour suppressor genes being essential in preservation of genome integrity
One strong candidate for genetic susceptibility factor to familial and/or sporadic breast cancer is the TP53 gene. This gene is frequently somatically mutated in breast cancer [6,7] and TP53 germline mutations are associated with increased risk for developing diverse malignancies, including 25–30% of hereditary breast cancer cases associated with Li-Fraumeni syndrome [8]
The distribution of the genotype frequencies in PIN3 Ins16bp polymorphisms among control group (p = 0.478) and in Arg72Pro and PIN3 Ins16bp among control subgroup (p = 0.082 and p = 0.294) is in agreement with those expected under Hardy-Weinberg equilibrium, excepted for Arg72Pro in the overall control group (p = 0.013)

Summary

Introduction

TP53 is one of major tumour suppressor genes being essential in preservation of genome integrity. 10% of all breast cancer cases exhibit a familial pattern of incidence [4,5] In this way, the remaining familial and sporadic risk may be due to common low to moderate penetrance genetic variants, which are referred as genetic polymorphisms. One strong candidate for genetic susceptibility factor to familial and/or sporadic breast cancer is the TP53 gene. This gene is frequently somatically mutated in breast cancer [6,7] and TP53 germline mutations are associated with increased risk for developing diverse malignancies, including 25–30% of hereditary breast cancer cases associated with Li-Fraumeni syndrome [8]. Based on its pivotal role in DNA damage repair and its physical and functional interactions with BRCA1 and BRCA2 proteins [9,10], TP53 seems to be a strong candidate breast cancer predisposition

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