Background and aim
Ototoxicity is a potential adverse effect of chemotherapy with platin drugs, such as cisplatin and carboplatin, in children. Hearing loss (HL) affecting frequencies below 4 kHz can compromise speech perception. The aim of this study was to investigate whether genetic variants previously implicated in ototoxicity are associated with HL overall and HL below 4 kHz in pediatric oncology patients treated with cisplatin or carboplatin.
Materials and methods
Patients given cisplatin or carboplatin for a pediatric cancer at least 5 years prior to the start of the study were enrolled. The patients underwent comprehensive audiological evaluations and genotyping to detect the presence of the GJB2 c.35delG, GSTP1 c.313A>G, and MT-RNR1 m.1555A>G polymorphisms.
HL was identified in 31/61 patients (50.8%), including 28/42 treated with cisplatin (66.6%) and 3/19 treated with carboplatin (15.8%). HL was associated with higher mean doses of cisplatin (p = .002) and carboplatin (p = .010). The c.313A>G variant of GSTP1 (heterozygous or homozygous) was detected in 31/61 patients (50.8%). An association between this variant allele and HL involving frequencies ≤ 4 kHz was identified (p = .020; 10-fold vs. non-carriers). No associations with HL were observed for GJB2 or MT-RNR1 gene variants.
The GSTP1 c.313A>G variant may increase the risk of low-frequency HL in pediatric oncology patients treated with cisplatin or carboplatin chemotherapy.
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The authors would like to acknowledge Dr. Sami Liberman and Vinicius Calsavara for their support on the statistical analysis.
Conflict of interest
The authors have no conflicts to declare.
This research involved human participants and it was approved by the Ethics Committee of Hospital AC Camargo Cancer Center under the protocol
Patients signed its informed consent.
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Liberman, P.H.P., Goffi-Gomez, M.V.S., Schultz, C. et al. Contribution of the GSTP1 c.313A>G variant to hearing loss risk in patients exposed to platin chemotherapy during childhood. Clin Transl Oncol 21, 630–635 (2019). https://doi.org/10.1007/s12094-018-1964-7
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