The influence of the Ataxia-Telangiectasia mutated G5557A polymorphism on cervical cancer development

Abstract

Introduction: DNA double strand break (DSBs) is one of the most serious threats to the integrity of the eukaryotic genome. One key protein that responds rapidly to this threat is Ataxia-Telangiectasia Mutated (ATM) protein kinase. Integration of Human Papillomavirus (HPV) DNA into the host genome is recognized as an essential step for the cell transformation and cervical cancer development. The aim of this study was to analyse the role of the ATM G5557A polymorphism in cervical cancer development. Material and Methods: We developed a retrospective study considering 484 cervical specimens of women from the northern Region of Portugal, using a real-time polymerase chain reaction methodology (assay C__26487857_10). Statistical analysis was performed using SPSS software. Results: No statistically significant differences were found, regarding the influence of the G5557A polymorphism with cytological classification, the presence or absence of HPV16 or other oncogenic high-risk HPV types (p>0.050). However, the ATM 5557A allele was found to influence the age at which the progression from LSIL to high-grade or invasive cervical cancer occurs (43.0 vs 59.0 years old; p=0.001). Conclusion: Our study reveals, for the first time, that ATM 5557A allele may influence cellular transformation leading low-grade lesions to progress to high-grade or invasive cervical cancer.