Glutathione S-transferase genetic polymorphisms and individual sensitivityto the ototoxic effect of cisplatin

One of the side effects of cisplatin therapy in malignant neoplasms is otot oxicity, This effect shows a wide interindividual range which is more varia ble than the pharmacokinetic parameters, Oxidative stress has been implicat ed in cisplatin ototoxicity, The glutathione S-transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress, Certain GST loci are polymophic, demonstrating alleles th at are null (GSTM1 and GSTT1), encode tow-activity variants (GSTP1) or are associated with variable inducibility (GSTM3), The aim of our study was to investigate genetic risk factors involved in the ototoxicity of cisplatin a nd to determine whether the polymorphisms in five GST genes affect the indi vidual risk of ototoxicity by cisplatin. Two groups of patients were analyz ed in this study: group H, 20 patients early and highly sensitive to the ot otoxicity of cisplatin; and group N, 19 patients with no hearing impairment under comparable doses of the drug. We found a protective effect for the G STM3*B allele with a frequency of 0.18 in the group with normal hearing aft er therapy versus 0.025 In the group with hearing impairment. (chi(2)=5.37; p=0.02), [(C) 2000 Lippincott Williams & Wilkins.].