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Contribution of the GSTP1 c.313A>G variant to hearing loss risk in patients exposed to platin chemotherapy during childhood

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Abstract

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.

Results

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.

Conclusion

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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Acknowledgements

The authors would like to acknowledge Dr. Sami Liberman and Vinicius Calsavara for their support on the statistical analysis.

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Authors and Affiliations

  1. Audiology Department, AC Camargo Cancer Center, r. Antonio Prudente, 211, São Paulo, 01509-900, Brazil

    P. H. P. Liberman, M. V. S. Goffi-Gomez & C. Schultz

  2. Human Molecular Genetics Laboratory, Molecular Biology and Genetic Engineering Center, CBMEG, State University of Campinas (UNICAMP), Campinas, Brazil

    P. L. Jacob & E. L. Sartorato

  3. Genomics and Molecular Biology Laboratory, International Research Center/CIPE, AC Camargo Cancer Center, São Paulo, Brazil

    C. A. A. de Paula, G. T. Torrezan, E. N. Ferreira & D. M. Carraro

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  1. P. H. P. Liberman
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Correspondence to M. V. S. Goffi-Gomez.

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This research involved human participants and it was approved by the Ethics Committee of Hospital AC Camargo Cancer Center under the protocol

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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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