[Genetic background of cisplatin induced ototoxicity].
BACKGROUND
Cisplatin induced ototoxicity is a serious adverse effect of cisplatin therapy. Cisplatin induced ototoxicity shows significant interindividual variability. This variability is probably based on genetic background. Recent papers describe association of cisplatin ototoxicity with allelic variants of glutathion-S-transferase coding genes.


METHODS
We have analyzed 55 patients treated with cisplatin therapy without any previous hearing impairment. Audiometric examination was performed before the start of cisplatin therapy and then before and after each cycle of cisplatin. DNA isolated from peripheral blood samples was used to analyze genetic polymorphisms of selected genes coding for glutathion-S-transferases.


RESULTS
We have demonstrated association of early onset of cisplatin induced hearing impairment with absence of null allele of GSTT1 (p = 0.009). Both GSTM1 gene deletion and single nucleotide polymorphism in GSTP1 gene (rs1695) did not show any association with cisplatin induced ototoxicity.


CONCLUSIONS
Early onset of cisplatin induced hearing impairment is more probable in persons with two functional alleles of GSTT1 gene.
Ústav patologické fyziologie, LF MU Brno. mjuraj@med.muni.cz
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M
Jurajda
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Talach
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Kostřica
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Lakomý
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Kocák
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Cvanová
D000970:Antineoplastic Agents / Q000009:adverse effects*; D001301:Audiometry, Pure-Tone; D002945:Cisplatin / Q000009:adverse effects*; D005982:Glutathione Transferase / Q000235:genetics*; D034381:Hearing Loss / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D011110:Polymorphism, Genetic
D000970:Antineoplastic Agents; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D002945:Cisplatin