GSTM1 null and GSTT1 null: predictors of cisplatin-caused acute ototoxicity measured by DPOAEs

AbstractPreventing the ototoxicity caused by cisplatin is a major issue yet to be overcome. Useful preventive treatments will soon be available. Consequently, the next step is to filter out those patients who are more prone to develop ototoxicity. The aim of this study was to prospectively evaluate potential predictive markers of acute ototoxicity as determined by measures of distortion product otoacoustic emissions (DPOAEs). A total of 118 patients from our previous DPOAE analysis were put under evaluation. Ototoxic cases were divided according to unilateral (n = 45) or bilateral (n = 23) involvement. The clinicopathological characteristics, hearing test results, germlineGSTT1,GSTM1, andGSTP1 polymorphisms, and common laboratory parameters were included in the new analysis. Univariate and multivariate statistical tests were applied. According to multivariate logistic regression, the only independent predictor of unilateral ototoxicity (vs. non-affected) was aGSTM1 null genotype (OR = 4.52; 95%CI = 1.3 –16.3), while for bilateral damage, theGSTT1 null genotype (OR = 4.76; 1.4 –16) was a predictor. The higher starting serum urea level was characteristic of bilateral ototoxicity; however, the only independent marker of bilateral (vs. unilateral) ototoxicity was the presence ofGSTT1 null genotype (OR = 2.44; 1.23 –4.85). Different processes, involving theGSTM1 andGSTT1 genotypes, respectively, govern the development of acute unilateral and bilateral ototoxicities. Further ...
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research