The role of glutathione S-transferase omega gene polymorphisms in childhood acute lymphoblastic leukemia: a case-control study

摘要

Background:Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Glutathione-S-methyl transferase (GSTs) enzymes’ family is known to catalyze carcinogens detoxification. Overexpression of (GSTO) omega class was reported in cancer occurrence. The purpose of the study was to investigate the association of GSTO1*A140D (rs4925) and GSTO2*N142D (rs156697) polymorphisms with the susceptibility to childhood ALL and to evaluate their prognostic impact. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism technique in 96 Egyptian pediatric?ALL patients and 99 controls.ResultsNo statistically significant different GSTO1*A140D genotype and allele distribution was observed among ALL cases and controls; however, a statistically significant different GSTO1*A140D genotype distribution was found between de novo ALL cases and controls [CC (37% vs. 56.6%), CA (47.8% vs. 40.4%), and AA (15.2% vs. 3.0%), respectively] (0.008). GSTO1*A140D variant genotypes’ frequency was significantly higher in de novo cases than in controls (63% vs. 43.4%) (0.028). The minor allele frequency (MAF) of GSTO1*A140D-A was significantly higher in de novo cases compared to controls (0.39 vs. 0.23) (0.005). Genotyping of GSTO2*N142D revealed a statistically significant difference of genotype distribution between ALL patients and controls [AA (26% vs. 36.3%), AG (62.5% vs. 61.6%), and GG (11.4% vs. 2.0%), respectively] (0.017) and between de novo ALL cases and controls [AA (37% vs. 36.3%), AG (45.7% vs. 61.6%), and GG (17.3% vs. 2.0%), respectively] (0.002). The MAF of GSTO2*N142D-G was significantly higher in ALL patients than in controls (0.42 vs. 0.32) (0.046). The high-risk ALL group had a higher frequency of GSTO1*A140D and GSTO2*N142D variant genotypes compared to corresponding wild genotypes and a higher frequency of combined polymorphisms compared to single polymorphisms and wild genotypes but with no statistically significant difference.ConclusionA statistically significant difference of GSTO1*A140D and GSTO2*N142D genotype distribution was detected between de novo ALL cases and controls. Compared to the control group, the MAF of GSTO1*A140D-A was overexpressed in de novo ALL cases and that of GSTO2*N142D-G was significantly higher in ALL patients. These findings suggest that the studied polymorphisms might play a significant role in the susceptibility to de novo childhood ALL in Egypt; however, GSTO1*A140D and/or GSTO2*N142D polymorphisms have no impact on ALL prognosis.