Glutathione S-transferase P1 polymorphism (Ile105Val) predicts cumulative neuropathy in patients receiving oxaliplatin-based chemotherapy.
Article Details
- CitationCopy to clipboard
Lecomte T, Landi B, Beaune P, Laurent-Puig P, Loriot MA
Glutathione S-transferase P1 polymorphism (Ile105Val) predicts cumulative neuropathy in patients receiving oxaliplatin-based chemotherapy.
Clin Cancer Res. 2006 May 15;12(10):3050-6. doi: 10.1158/1078-0432.CCR-05-2076.
- PubMed ID
- 16707601 [ View in PubMed]
- Abstract
PURPOSE: Glutathione S-transferases (GST) are xenobiotic metabolizing enzymes involved in the detoxification of a variety of chemotherapeutic drugs, including platinum derivatives. Genetic polymorphisms of GSTs have been associated with enzyme activity variations. Thus, a study was done to investigate the relationship between GST polymorphisms and oxaliplatin-related cumulative neuropathy in gastrointestinal cancer patients treated with oxaliplatin-based chemotherapy. EXPERIMENTAL DESIGN: Ninety patients were included. Clinical neurologic evaluation was done at baseline and before each cycle of treatment. We determined genetic variants for GSTP1 exon 5 (Ile105Val), GSTP1 exon 6 (Ala114Val), GSTM1 (homozygous deletion), and GSTT1 (homozygous deletion). We conducted analyses in a subgroup of 64 patients receiving a minimal cumulative dose of 500 mg/m2 of oxaliplatin to examine whether the GST polymorphisms are associated with oxaliplatin-related cumulative neuropathy. RESULTS: Among patients receiving a minimal cumulative dose of 500 mg/m2 of oxaliplatin, 15 patients showed clinically evident oxaliplatin-related cumulative neuropathy scored grade 3 according to an oxaliplatin-specific scale. The oxaliplatin-related cumulative neuropathy scored grade 3 was significantly more frequent in patients homozygous for the GSTP1 105Ile allele than in patients homozygous or heterozygous for the GSTP1 105Val allele (odds ratio, 5.75; 95% confidence interval, 1.08-30.74; P = 0.02). No association was found with respect to any of the GSTM1, GSTT1, or GSTP1 exon 6 genotypes. CONCLUSIONS: The results of the current study suggest that the 105Val allele variant of the GSTP1 gene at exon 5 confers a significantly decreased risk of developing severe oxaliplatin-related cumulative neuropathy.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Oxaliplatin Glutathione S-transferase Mu 1 Protein Humans NoSubstrateDetails Oxaliplatin Glutathione S-transferase P Protein Humans NoSubstrateDetails Oxaliplatin Glutathione S-transferase theta-1 Protein Humans NoSubstrateDetails