Associations between glutathione S-transferase π Ile¹⁰⁵Val and glyoxylate aminotransferase Pro¹¹Leu and Ile³⁴⁰Met polymorphisms and early-onset oxaliplatin-induced neuropathy

Abstract 

Purpose: Although the risk of oxaliplatin-induced neuropathy depends on cumulative oxaliplatin dose, susceptibility to this adverse event differs greatly among patients. In this study, we investigated the associations between oxaliplatin-induced neuropathy and the following polymorphisms: glutathione S-transferase π (GSTP1) Ile¹⁰⁵Val, and glyoxylate aminotransferase (AGXT) Pro¹¹Leu and AGXT Ile³⁴⁰Met. Experimental design: Eighty-two Japanese patients with histologically confirmed colorectal cancer who received at least six cycles of the modified FOLFOX6 (m-FOLFOX6) regimen were enrolled. To minimize differences in cumulative oxaliplatin dose between patients, oxaliplatin-induced neuropathy was evaluated using an oxaliplatin-specific scale during the 2-week period after completion of the sixth cycle of treatment. Results: Forty-four patients developed grade 2/3 oxaliplatin-induced neuropathy. There were more patients carrying at least one GSTP1 ¹⁰⁵Val allele among the group with grade 2/3 neuropathy (18/44, 41%) than among the group with grade 1 neuropathy (9/38, 24%), although the difference was not statistically significant (P=0.098). There were similar numbers of patients carrying at least one AGXT ¹⁰⁵Met allele in the grade 2/3 neuropathy (7/44, 16%) and grade 1 neuropathy groups (5/38, 13%; P=0.725). The AGXT ¹¹Leu allele was not found in any of our patients or controls. Conclusions: We found no significant association between oxaliplatin-induced neuropathy and the GSTP1 Ile¹⁰⁵Val and AGXT Ile³⁴⁰Met polymorphisms. Given that no AGXT ¹¹Leu allele was found among our study population (n=177), evaluating this polymorphism in Japanese patients in future studies is likely to be uninformative.

Keywords: Oxaliplatin, Neurotoxicity, Colorectal cancer, GSTP1 Ile¹⁰⁵Val, AGXT Pro¹¹Leu, AGXT Ile³⁴⁰Met