Investigation of oxidative stress and mononuclear leukocyte DNA damage in idiopathic granulomatous mastitis patients

Objective: Idiopathic granulomatous mastitis (IGM) is a rare, chronic inflammatory disease of the breast, the etiology of which has not been clearly clarified. Although it is a benign disease, it is sometimes complicated and resistant to treatment and may progress with relapses. Many factors, including autoimmunity, have been mentioned in the etiology. IGM is particularly important because it requires a differential diagnosis from breast cancer based on clinical and radiological findings, and although it is considered a benign breast disease due to its tendency to become chronic, it negatively affects the quality of life of patients. The incidence of idiopathic granulomatous mastitis in our country and the studies on this subject are higher than in other countries. In the literature, there is no study evaluating IGM together with DNA damage and oxidative stress. The aim of this project is to investigate whether IGM disease causes oxidative stress and DNA damage. Demonstrating the presence of DNA damage and oxidative stress in this disease, which does not have a clear scheme in the treatment protocol will allow alternative treatment options that prevent DNA damage caused by oxidative stress and may be a guide in the development of treatment protocols. Material and Methods: The study included 28 patients who applied to Bezmialem Vakıf University Faculty of Medicine Hospital General Surgery Clinic and Istanbul University-Cerrahpaşa Medical Faculty Granulomatous Mastitis Polyclinic between October 2023 and October 2024, were diagnosed with granulomatous mastitis, confirmed clinically and histopathologically, and deemed idiopathic due to the absence of any identified etiology. These patients had not received corticosteroid or immunosuppressive therapy in the last 6 months. Additionally, 27 healthy women of similar age to the patient group were included int he study. The study was approved by the Ethics Committee of Bezmialem Vakif University Faculty of Medicine. In addition to the routine blood taken from IGM patients during outpatient clinic admission, 10cc venous blood and urine samples were taken into an EDTA tube under sterile conditions and brought to the laboratory. Mononuclear leukocyte DNA damage, total antioxidant level (TAS) and total oxidant level (TOS) analyzes were performed from these blood and urine samples. Oxidative stress index (OSI) was calculated. Sociodemographic data, laboratory and imaging results of the patients were also evaluated. Results: The mean age of the patients included in the study was 37.3±5.3 years, while the mean age of the healthy volunteer group was 35.4±8.6 years. The age of the patients did not differ significantly between the control and patient groups (p=0.081). Blood and urine samples were collected for the study, and hemogram, biochemistry, and serology values measured during the same period or within one month were also recorded. Leukocyte, neutrophil, lymphocyte values, neutrophil/lymphocyte ratio, Urea, Creatinine, LDH and Potassium values were significantly (p<0.05) higher in the patient group than in the control group. In the patient group, leukocyte, neutrophil, lymphocyte counts, neutrophil/lymphocyte ratio, urea, creatinine, LDH, and potassium levels were significantly higher than the control group (p<0.05). CRP and Sedimentation values were also analyzed in the patient group. The mean CRP and sedimentation values were 23.78 and 20.62 respectively, which were in the upper limit of normal. TOS, OSI and Urine 8-Hydroxydeoxyguanosine values in the patient group were significantly higher than the control group. (p=0.009; p=0.028; p=0.024). TAS value did not differ significantly between the control and patient groups. (p=0.534) In Comet Assay analysis for DNA damage, tail intensity percentage and tail moment value were significantly higher in the patient group than in the control group. (p=0.029; p=0.016) Conclusion:This study investigated oxidative stress and mononuclear leukocyte DNA damage in Idiopathic Granulomatous Mastitis (IGM) patients. The results revealed that IGM patients exhibited increased Total Oxidant Status (TOS), elevated urinary 8-OHdG levels, and significantly higher Oxidative Stress Index (OSI) and oxidative pressure. To assess DNA damage, parameters of DNA fragments were measured using the Comet Assay, a recognized method for detecting DNA damage; the tail moment and tail intensity ratios were found to be significantly higher. Considering these findings, reducing free radical production and slowing DNA damage could provide an alternative treatment modality for IGM patients. The use of natural or synthetic antioxidants may be an option in the treatment of the disease. Keywords: Idiopathic granulomatous mastitis, Oxidative stress, DNA damage