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

Glutathione S-transferases (GSTs) have been associated with outcome in huma n cancers treated with cytotoxic chemotherapy. In a case control study, we investigated the association between polymorphisms within the GSTM1, GSTT1, and GSTP1 genes and risk of relapse in childhood acute lymphoblastic leuke mia (ALL). Cases were relapsed patients. Controls were successfully treated patients with a minimum follow-up of 5 years. The null genotype (absence o f both alleles) for GSTM1 or GSTT1 conferred st 2-fold (OR = 0.5, 95% Ct = 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 GSTP1 Val(105)/Val(105) genotype showed a 3-fold decrease in risk of relapse (OR = 0.33, 95% CI = 0.09-1.23, P = .099) in co mparison to the combined category of Ile(105)/Val(105) and Ile(105)/Ile(105 ) genotypes. No particular associations with relapse were observed for the GSTP1 polymorphism at codon 114. The risk of relapse when having 1 of the l ow-risk genotypes (GSTM1 null, GSTT1 null, GSTP1 Val(105)/Val(105)) decreas ed 1.9-fold (OR = 0.53, 95% CI = 0.24-1.19, P = .123), and the risk when ha ving 2 or 3 law-risk genotypes 3.5-fold (OR=0.29, 95% CI = 0.06-1.37, P=.11 8), compared with individuals having no low-risk genotype (P far trend =.00 5). Our results suggest that polymorphisms within genes of the GST superfam ily may be associated with risk of relapse in childhood ALL. (Blood. 2000;9 5:1222-1228) a 2000 by The American Society of Hematology.