Glutathion-S-Transferases (GSTs) polymorphisms modify the risk of relapse in Argentine pediatric patients with Acute Lymphoblastic Leukemia

COTIGNOLA J; RICCHERI C; LEONARDI D; DE SIERVI A; FARFAN P; ALFONSO G; VAZQUEZ E

Santiago

Congreso; 8th BIENNIAL CHILDHOOD LEUKEMIA SYMPOSIUM 2012; 2012

Acute Leukemia (AL) is the most common cancer in children world-wide. The Argentine Hospital Oncopediatric Registry (ROHA) estimated that 469 children are newly diagnosed with AL every year and that the 80% corresponds to Acute Lymphoblastic Leukemia (ALL). Even though an enormous progress was achieved in the survival rate of childhood ALL, some cases still relapse or have a fatal outcome. Genetic polymorphisms account, at least in part, for differences in disease outcome, response to treatment, and development of therapy-related toxic side effects. Therefore, our goal is to identify genetic markers that help to better predict childhood ALL outcome. To accomplish this, we recruited pediatric patients diagnosed with ALL from one Hospital Center in Buenos Aires. The protocol was approved by the Ethic Committee and follows the ethical principles enunciated by the Declaration of Helsinki. Patients’ relatives or guardians signed an informed consent before sample donation. We draw peripheral blood and extracted lymphocyte DNA. We genotyped polymorphisms in three glutathione-S-transerase genes (GSTP1 c.313 A>G (p.105 Ile>Val), GSTT1 null, and GSTM1 null). GSTT1 and GSTM1 polymorphisms were assessed by PCR multiplex, and GSTP1 c.313 A>G by PCR-RFLP. We performed Kaplan-Meier (KM) survival analyses and univariate Cox regression models to study the association between these polymorphisms and ALL relapse, and to estimate Hazard Ratios (HR) and 95% Confidence Intervals (95%CI). KM analyses of 131 pediatric ALL samples showed that patients with the GSTP1 c.313 GG genotype (p.105 Val/Val) had poorer relapse-free survival (RFS) (KM log-rank p=0.03; Cox HR=3.5; 95%CI=1.02-12.01). Similarly, when we combined the genotype of the three genes we found that patients with more variant alleles had shorter RFS (KM log-rank p=0.03; Cox HR=4.9; 95%CI=0.94-25.32). Our findings show that GSTs polymorphisms modify the risk of ALL relapses in Argentine patients, and might become a tool to personalize treatment and follow-up schemas.