Polymorphisms within glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a case-control study

Abstract

Glutathione S-transferases (GSTs) have been associated with outcome in human cancers treated with cytotoxic chemotherapy. In a case-control study, we investigated the association between polymorphisms within theGSTM1, GSTT1, and GSTP1 genes and risk of relapse in childhood acute lymphoblastic leukemia (ALL). Cases were relapsed patients. Controls were successfully treated patients with a minimum follow-up of 5 years. The null genotype (absence of both alleles) for GSTM1 or GSTT1 conferred a 2-fold (OR = 0.5, 95% CI = 0.23-1.07, P = .078) and 2.8-fold (OR = 0.36, 95% CI = 0.13-0.99, P = .048) reduction in risk of relapse, respectively, relative to the presence of the GSTM1 or GSTT1 gene. The GSTP1Val105/Val105 genotype showed a 3-fold decrease in risk of relapse (OR = 0.33, 95% CI = 0.09-1.23,P = .099) in comparison to the combined category of Ile105/Val105 and Ile105/Ile105 genotypes. No particular associations with relapse were observed for the GSTP1polymorphism at codon 114. The risk of relapse when having 1 of the low-risk genotypes (GSTM1 null, GSTT1 null,GSTP1 Val105/Val105) decreased 1.9-fold (OR = 0.53, 95% CI = 0.24-1.19, P = .123), and the risk when having 2 or 3 low-risk genotypes 3.5-fold (OR = 0.29, 95% CI = 0.06-1.37, P = .118), compared with individuals having no low-risk genotype (P for trend = .005). Our results suggest that polymorphisms within genes of the GST superfamily may be associated with risk of relapse in childhood ALL.