 - Genetic factors predisposing to or protecting against the toxicity of platinum derivatives Several GST isoenzymes present polymorphisms modifying their activity. This is the case for the GSTM1 and GSTT1 isoenzymes, which can undergo deletions responsible for loss of activity of the enzyme, and GSTM3, for which the GSTM3B allele has been associated with induction of enzyme activity by cisplatin Peters et al., 2000. An AG polymorphism situated in the substrate binding domain of the GSTP1 isoenzyme in position 313 of exon 5 A313G induces substitution of a isoleucine by a valine Ile105Val. This polymorphism is relatively frequent about 10 of homozygous mutants in Caucasian populations. It influences the activity of the enzyme and has been associated with better survival of patients receiving platinum-based chemotherapy Goekkurt et al., 2006; Stoehlmacher et al., 2002; Sun et al., 2009. This polymorphism has also been shown to influence the toxicity of platinum-based treatments. For example, one study showed that the neurotoxicity of oxaliplatin was more frequent in subjects homozygous for GSTP1 105Ile allele than in heterozygous subjects or subjects homozygous for the GSTP1 105Val allele odds ratio 5.75. Lecomte et al., 2006. This protective effect of the mutant allele has also been demonstrated for docetaxel peripheral neuropathies odds ratio 6.11 and cisplatin ototoxicity in testicular cancers in young men Mir et al., 2009; Oldenburg et al., 2007. 