Cisplatin-induced long-term hearing impairment is associated with specific glutathione S-transferase genotypes in testicular cancer survivors

Abstract

Purpose: Cisplatin, a cornerstone of combination chemotherapy in the treatment of testicular cancer, induces hearing impairment with considerable interindividual variations. These differences might be a result of functional polymorphisms in cisplatin-detoxifying enzymes like glutathione S-transferases (GSTs). Patients and Methods: We identified 173 cisplatin-treated testicular cancer survivors (TCSs) who had participated in a long-term survey that included audiometric testing and lymphocyte sampling. The hearing decibel thresholds at 4,000 Hz were categorized into leveled scales by normative decibel percentiles. Known functional polymorphisms (positive or negative) in GSTT1 and GSTM1 and codon 105 A/G (Ile/Val) in GSTP1 were analyzed by multiplex polymerase chain reaction, followed by restriction enzyme cutting, and separated by gel electrophoresis. Results: The risk of having an inferior audiometric result was more than four times higher in TCSs with 105Ile/105Ile- GSTP1 or 105Val/105Ile-GSTP1 compared with 105Val/105Val-GSTP1 (odds ratio [OR] = 4.21; 95% CI, 1.99 to 8.88; P < .001, OLR). Conclusion: The presence of both alleles of 105Val-GSTP1 offered protection against cisplatin-induced hearing impairment. Two genotype patterns with good and poor protection against cisplatin-induced ototoxicity were identified. © 2007 by American Society of Clinical Oncology.