Contribution of the GSTP1 c.313A>G variant to hearing loss risk in patients exposed to platin chemotherapy during childhood
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.
KeywordsHearing loss Cancer Ototoxicity Cisplatin Carboplatin GSTP1
The authors would like to acknowledge Dr. Sami Liberman and Vinicius Calsavara for their support on the statistical analysis.
Compliance with ethical standards
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.
- 1.Brock PR, Yeomans EC, Bellman SC, Pritchard J. Cisplatin therapy in infants: short and long-term morbidity. Br J Cancer Suppl. 1992;18:S36–40.Google Scholar
- 12.Peters U, Preisler-Adams S, Lanvers-Kaminsky C, Jürgens H, Lamprecht-Dinnesen A. Sequence variations of mitochondrial DNA and individual sensitivity to theototoxic effect of cisplatin. Anticancer Res. 2003;23:1249–55.Google Scholar
- 15.Hu X, Xia H, Srivastava SK, Pal A, Awasthi YC, Zimniak P, Singh SV. Catalytic efficiencies of allelic variants of human glutathione S-transferase P1-1 toward carcinogenic anti-diol epoxides of benzo[c] phenan-threne and benzo[g]chrysene. Cancer Res. 1998;58:5340–3.Google Scholar
- 16.Brock PR, Knight KR, Freyer DR, Campbell KC, Steyger PS, Blakley BW, Rassekh SR, Chang KW, Fligor BJ, Rajput K, Sullivan M, Neuwelt EA. Platinum-induced ototoxicity in children: a consensus review on mechanisms, predisposition, and protection, including a new International Society of Pediatric Oncology Boston ototoxicity scale. J Clin Oncol. 2012;30(19):2408–17. https://doi.org/10.1200/JCO.2011.39.1110.CrossRefGoogle Scholar
- 17.Liberman PHP, Goffi-Gomez MVS, Schultz C, Lopes LF. What are the audiometric frequencies affected are the responsible for the hearing complaint in the hearing loss for ototoxicity after the oncological treatment? Arq Int Otorrinolaringol. 2012;16:26–31.Google Scholar
- 22.Jerónimo C, Varzim G, Henrique R, Oliveira J, Bento MJ, Silva C, Lopes C, Sidransky D. I105V polymorphism and promoter methylation of the GSTP1 gene in prostate adenocarcinoma. Cancer Epidemiol Biomark Prev. 2002;11(5):445–50.Google Scholar
- 23.Jehanne M, Lumbroso-Le Rouic L, Savignoni A, Aerts I, Mercier G, Bours D, Desjardins L, Doz F. Analysis of ototoxicity in young children receiving carboplatin in the context of conservative management of unilateral or bilateral retinoblastoma. Pediatr Blood Cancer. 2009;52(5):637–43. https://doi.org/10.1002/pbc.21898.CrossRefGoogle Scholar
- 28.ABraOM: Brazilian genomic variants. http://abraom.ib.usp.br.