Polimorfismos nos genes TP53, 53BP1 e ATM: Susceptibilidade para cancro do colo do útero

• Main Author: Oliveira, Sara Raquel da Silva
• Publication Date: 2007
• Format: Master thesis
• Language: por
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: http://hdl.handle.net/10216/7616
• topic: Medicina e Oncologia Molecular; Porto

Cell cycle progresses without interruptions. However, when DNA damage occurs, namely double strand breaks, cells are able to stops transiently her proliferation. In response to this threat, eucariotic cells develop mechanisms, which detect this damage DNA. Thereby generally this DNA can be repaired. The kinase protein, pATM, carries out this response. Upon identification of the damage DNA, pATM is activated and fosforilates a set of proteins involved in cell cycle. One of these proteins is p53, which have been associated with the development of almost all type of human tumours. Other essencial protein in cellular response to double strand breaks is p53BP1. However, the exactly mechanism of this protein in cell cycle remains controversial. We developed a retrospective study considering a total of 700 cervical specimens of women from Northern region of Portugal, in order to evaluate the influence of genetic polymorphisms in TP53, 53BP1 and ATM genes in cervical cancer susceptibility. Actually is known that for the development of this neoplasia, the infection with human papillomavirus is a necessary condition perhaps not sufficient. Regarding the R72P polymorphisms in p53, no statistically significant differences were found. Therefore, at least in our population, the p53 R72P polymorphism is not associated with an increased susceptibility to squamous intraepithelial lesions or cervical cancer development (p>0.05). Analysing the C1236G polymorphism, we verify that the infection of HPV16 increases the risk of progression for high-grade squamous intraepithelial lesions in C carrier patients. Contrary, this effect in patients with GG genotype was not found (p=0.00002; OR=5.6 e p=0.299 respectively). The ATM 5557A allele was found to influence the age at which the progression from low-grade squamous intraepithelial lesions to high-grade squamous intraepithelial lesions or invase carcinoma occurs. The median age of onset cancer in ATM A allele carries was 43.0 years old comparing to 59.0 years old in G allele homozygous (p=0.001).