Improving risk strati cation of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse

RICCHERI MARIA; GERALDINE GUERON; COTIGNOLA JAVIER; ABBATE MERCEDES; GRACIELA ALFONSO; ELBA VAZQUEZ; DAIANA LEONARDI; MYRIAM NUÑEZ; ADRIANA DE SIERVI

Oncotarget

Impact Journals, LLC

Año: 2016

The inclusion of genotype at Acute Lymphoblastic Leukemia (ALL) diagnosis as a genetic predictor of disease outcome is under constant study. However, results are inconclusive and seem to be population speci c. We analyzed the predictive value of germline polymorphisms for childhood ALL relapse and survival. We retrospectively recruited 140 Argentine patients with de novo ALL. Genotypes were analyzed using PCR- RFLP (GSTP1 c.313A > G, MDR1 c.3435T > C, and MTHFR c.665C > T) and multiplex PCR (GSTT1 null, GSTM1 null). Patients with the GSTP1 c.313GG genotype had an increased risk for relapse in univariate (OR = 2.65, 95% CI = 1.03?6.82, p = 0.04) and multivariate (OR = 3.22, 95% CI = 1.17?8.83, p = 0.02) models. The combined genotype slightly increased risk for relapse in the univariate (OR = 2.82, 95% CI = 1.09?7.32, p = 0.03) and multivariate (OR = 2.98, 95% CI = 1.14?7.79, p = 0.03) models for patients with 2/3-risk-genotypes (GSTT1 null, GSTM1 null, GSTP1 c.313GG). The Recurrence-Free Survival (RFS) was shorter for GSTP1 c.313GG (p = 0.025) and 2/3-risk-genotypes (p = 0.021). GST polymorphisms increased the risk of relapse and RFS of patients with childhood ALL. The inclusion of these genetic markers in ALL treatment protocols might improve risk strati cation and reduce the number of relapses and deaths.