Effect of GST gene polymorphism on cisplatin caused acute ototoxic side effects
Prekopp Péter
Surgical Medicine Division
Dr. Szijártó Attila
SE Fül-Orr-Gégészeti és Fej-Nyaksebészeti Klinika tanterem
2026-11-02 13:00:00
Otorhinolaryngology
Dr. Tamás László
Dr. Gáborján Anita
Dr. Horváth Miklós
Dr. Magyar Márton
Dr. Holló Péter
Dr. Birtalan Ede
Dr. Majoros Attila
Dr. Móricz Péter
I joined our working group in 2003, when we were curious to see, through a retrospective study, after how many cycles does the ototoxic side effect of cisplatin occur. We
conducted our studies on testicular cancer patients treated with cisplatin because this is a young population treated with cisplatin-based chemotherapy, in whom age related hearing loss does not confound our results. We performed our hearing tests using
distortion product otoacoustic emission. This is a quick test and does not require an anechoic room. But its greatest advantage is that it examines the function of the outer hair cells, which are the most critical target of the ototoxic side effects of cisplatin. 223
patients were included in the study. The results showed that ototoxic side effects can be detected after 4 cycles, i.e. a total dose of 400mg/m2, years after treatment.
During our work, we noticed that, with significant individual differences, there are
patients who experience hearing problems even after one cycle of cisplatin treatment. Therefore, we designed a prospective study in which we measured DPOAE in patients immediately before and immediately after 1 cycle of cisplatin treatment. 137 patients
were involved. We investigated whether acute ototoxic side effects appear as a consequence of 1 cycle of cisplatin treatment. DPOAE measured before and after the first cycle of cisplatin at each frequency in right and left ear of patients resulted in significant differences 750, 6000 and 8000 Hz.
Subsequently, blood samples from 118 patients from this patient material were examined
for GST gene polymorphisms. Glutathione-s-transferase is a phase II degradation enzyme, which is responsible for the degradation of cisplatin, among others. Due to the different degradation dynamics of its different efficacy phenotypes, this may be the reason for the individual differences in ototoxic side effects experienced by patients.
Therefore, we examined the gene polymorphisms of the GSTP1, GSTM1 and GSTT1 enzymes in the 118 patients and based on this we created subgroups. The DPOAE results of the subgroups were compared. From our results we were able to conclude that, GSTM1 null and GSTT1 null genotypes proved to be statistically independent markers of unilateral and bilateral acute ototoxicity, respectively.
The a priori identification of a high-risk group can serve as a basis for a better definition of individualized treatment and the targeted use of new otoprotective drugs.
