ATM Polymorphisms and their Relationship to Radiation Toxicity in Breast Cancer Patients / Polimorfismos ATM e sua relação com a toxicidade por radiação em pacientes com câncer de mama

Abstract

The breast cancer is one of the most common types and it treatment brings complications such as skin, dermis and subcutaneous toxicity. Studies about genetic variations of patients are those that enable the identification of prognostic factors for treatment, generally based on greater risk of injury to healthy tissue. Study design: This study examined the association between single nucleotide polymorphisms (SNPs) of ATM gene in patients with breast cancer with adverse reactions presented in normal tissues as result of radiotherapy. Place and Duration of Study: The study was conduct at Pontifícia Universidade Católica de Goiás, and the patients were recruited at Hospital Araújo Jorge, Associação de Combate ao Câncer em Goiás, Radiotherapy Service. Methodology: We evaluated 76 patients, through a retrospective study, based on data contained in records and teletherapy records of patients with this cancer who underwent radiotherapy for at least 5 years. Polymorphisms of the ATM gene were analyzed by microarray technique. Results: The mean age of patients was 50 years and the total dose of radiation was an average of 50,21 Gy ranging from 45Gy to 50.4Gy. Regarding the late toxicities, patients analyzed showed a higher frequency of low-grade morbidities when compared to high grade. Nineteen patients interrupted the radiation therapy for any reason. Patients who have studied polymorphisms have no increased risk of developing acute toxicity changes of the skin. (P>.05). Patients presenting polymorphisms AX-8315255 (TTT insertion) (RR=11.0, 1.08 -111.97, p=0.045) and rs56128736 (RR=11.0, 1.08 -111.97, p=0.045) had an increased risk for developing late skin toxicity, but not at subcutaneous tract. Conclusion: ATM is a large gene with many variants documented. Association studies of these SNPs will be needed in larger sample groups to establish whether the single base variants or haplotypes of this gene may indeed contribute to the toxicity of normal tissue. Thus, the personalized treatment with ionizing radiation can be prescribed for patients decreasing complications and improving the effectiveness of treatment and quality of life of patients.