Research Information System
Thesis Type: Expertise In Medicine
Institution Of The Thesis: Gazi Üniversitesi, Tıp Fakültesi, Turkey
Approval Date: 2020
Thesis Language: Turkish
Student: BETÜL KARGI ÖZTURAN
Supervisor: FARUK GÜÇLÜ PINARLI
Abstract:Introduction: Ototoxicity, especially in childhood, is one of the most common side effects of these drugs. In our study, it was aimed to investigate the ototoxicity caused by platinum-based chemotherapy in our pediatric oncology discipline, to evaluate the risk factors and to determine the significance of polymorphism susceptibility to ototoxicity. Materials and Method: In this study, 34 patients and 100 healthy children treated with cisplatin / carboplatin in the pediatric oncology were retrospectively evaluated between October 2019 and January 2019. Hearing function of the patients was evaluated according to Brock grading scale by evaluating with OAE. The diagnosis of all patients, their age at diagnosis, the time after discontinuation of the drug, cumulative drug doses, additional ototoxic drugs were recorded and the relationship between these factors and hearing loss was evaluated. The DNAs of all patients and healthy children were isolated from whole blood samples and the susceptibility to develop ototoxicity was evaluated by studying GSTM3 (CTC/del) rs36120609, SLC31A1 (T>G) rs10981694, ACYP2 (G>A) rs1872328. In the control group, the frequency of these polymorphisms in the Turkish population was determined and its significant for the risk of ototoxicity was evaluated. 91 Results: Hearing in 24 patients (70%) in the study was normal (stage 0). Hearing loss was observed in 6 patients (17.4%) in grade 1, in 3 patients (9%) in patient grade 2, in 1 patient (3%) in grade 3. The cumulative dose of cisplatin was ≥ 400 mg/m² and the cumulative carboplatin dose was ≥ 1500 mg/m². The age, the age of diagnosis, and the time elapsed after taking medication were not significant in increasing the risk of hearing loss. In healthy Turkish children, the frequency of GSTM3 del allele was 13.5%, SLC31A1 G allele was 10.5%, and the ACYP2 gene A allele carrier was 5%. The frequency of GSTM3 del allele and SLC31A1 G allele were found to be higher in patients with hearing loss and in patients with normal hearing, respectively. However, these difference were not statistically significant. Conclusion: There was no significant relationship between gender, ≥400 mg / m² cisplatin and ≥1500 mg / m² carboplatin cumulative dose, being diagnosed under the age of 5, and the time after taking the drug. GSTM3, SLCL31A1 and ACYP2 genes had no statistically role in ototoxicity. However, the frequency of GSTM3 del allele was found to be higher in patients with hearing loss. The del allele was thought to increase the risk of ototoxicity after exposure to platinum, as a result of decreased detoxification efficiency of the GSTM3 gene. Also, the frequency of SLC31A1 G allele was increased in patients with normal hearing. It was thought that rs10981694 polymorphism might be preventive against ototoxicity by preventing cochlear uptake of platinum group drugs by disrupting CTR1 function