Document Detail

Cisplatin-induced ototoxicity in pediatric solid tumors: the role of glutathione S-transferases and megalin genetic polymorphisms.
MedLine Citation:
PMID:  23274376     Owner:  NLM     Status:  MEDLINE    
Cisplatin-induced ototoxicity, an important dose-limiting side effect, has proven high interindividual variability. Glutathione S-transferases (GSTs) are isoenzymes involved in cellular detoxification processes. Megalin has been demonstrated to bind aminoglycosides, known to be similar to cisplatin for their ototoxicity. The GSTs and megalin expression is genetically polymorphic, which might be responsible for the variability in cisplatin-induced ototoxicity. The genotyping of GSTM1, GSTT1 polymorphisms, and 2 nonsynonymous single nucleotide polymorphisms (SNPs) at megalin genes, rs2075252 and rs2228171, were performed in 68 children diagnosed with solid tumors who received cisplatin-based chemotherapy. After the end of treatment, audiometry demonstrated hearing loss in 79.4% of patients according to Brock classification. The cumulative cisplatin dose >400 mg/m is associated with increased risk of cisplatin-induced ototoxicity [odds ratio (OR), 17.5; 95% confidence interval (CI), 3.09-98.62]. GSTT1 wild genotype and C-allele of rs2228171 SNPs of megalin gene occurred with higher frequency in patients with ototoxicity (P=0.023; OR, 10; 95% CI, 1.80-56.00 and P=0.034; OR, 2.67; 95% CI, 1.22-5.82, respectively). In conclusion, our results suggested that GSTT1 wild genotype and C-allele of rs2228171 SNPs might be risk factors for ototoxicity. The cumulative cisplatin dose <400 mg/m should be beneficial in order to ameliorate ototoxicity.
Worawut Choeyprasert; Rachchadol Sawangpanich; Krisna Lertsukprasert; Umaporn Udomsubpayakul; Duantida Songdej; Usanarat Unurathapan; Samart Pakakasama; Suradej Hongeng
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pediatric hematology/oncology     Volume:  35     ISSN:  1536-3678     ISO Abbreviation:  J. Pediatr. Hematol. Oncol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-24     Completed Date:  2013-06-07     Revised Date:  2013-07-22    
Medline Journal Info:
Nlm Unique ID:  9505928     Medline TA:  J Pediatr Hematol Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e138-43     Citation Subset:  IM    
Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Bangkok, Thailand.
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MeSH Terms
Antineoplastic Agents / administration & dosage,  adverse effects
Child, Preschool
Cisplatin / administration & dosage,  adverse effects*
Glutathione Transferase / genetics*
Hearing Loss / chemically induced*,  genetics*
Low Density Lipoprotein Receptor-Related Protein-2 / genetics*
Neoplasms / drug therapy,  genetics*
Polymorphism, Single Nucleotide
Reg. No./Substance:
0/Antineoplastic Agents; 0/Low Density Lipoprotein Receptor-Related Protein-2; 15663-27-1/Cisplatin; EC 2.5.1.-/glutathione S-transferase T1; EC Transferase; EC S-transferase M1

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