O Papel dos Polimorfismos de Genes da Via de Reparo com a Radiotoxicidade em Pacientes com Câncer de Cólo Uterino

Abstract

In Brazil, cervical cancer is the second most common among women. Radiation therapy is part of its interdisciplinary management, playing an important role in their loco regional control. The major challenge of modern medicine in radiotherapy is to develop predictive methods that can determine the level of radiosensitivity of the patient and the healthy surrounding tissue in order to individualize the prescribed radiation dose, to prevent severe side effects and promoting better local tumor control. This study evaluated the acute and chronic adverse effects on the skin, lower gastrointestinal tract and urinary tract of radiotherapy in 47 cervical cancer patients. Methods and Materials: Biological material was collected and DNA from peripheral blood was extracted of all patients studied. The fragments of TP53 and ATM were amplified to be sequenced, to verify if there are any polymorphisms witch could be responsible to the radiosensitivity of the patients. Results and Discussion: In a univariate analysis, the variable age was strongly associated with a risk of acute toxicity skin (p=0,023). Patients that received a high dose of external beam radiation and patients who have undergone brachytherapy, showed a significantly higher incidence of chronic urinary tract toxicity (p=0,031) and (p=0,019), respectively. The exchange G>A in the position 5557 of the ATM gene was significantly associated with the risk of acute lower gastrointestinal tract (p=0,008). There wasn t association between the other TP53 polymorphisms analyzed and the frequency of side effects (p>0,05). Our data revealed that patients who evolved significant association presented death (p=0,019) with the increase of chronic skin radiossensitivity. Conclusions: These observations corroborate the importance of investigating the genetic profile to predict adverse side effects in cervical cancer patients undergoing radiotherapy. These genes have an important role in DNA repair pathways and probably are capable of modifying the responses of normal tissues to radiotherapy.