GSTT1 null and rs156697 Polymorphism in GSTO2 Influence the Risk and Therapeutic Outcome of B-Acute Lymphoblastic Leukemia Patients

Glutathione S-transferase (GST) gene deletion or polymorphic sequence variations lead to decreased enzyme activity that influences susceptibility and response to chemotherapy in acute lymphoblastic leukemia (ALL). This case-control study investigated the association of GST gene polymorphisms with the etiology and therapeutic outcome of B-ALL among Kashmiri population. A total of 300 individuals including 150 newly diagnosed B-ALL patients and an equal number of age and gender matched controls were genotyped for five GST gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP) and multiplex PCR techniques. Higher frequency of , AG, and GG genotypes was observed in ALL cases compared to controls that associated significantly with ALL risk ( OR = 2.93, = 0.0001; AG: OR = 2.58, = 0.01; -GG: OR = 3.13, = 0.01). , , and SNPs showed no significant association ( 0.05). Combined genotype analysis revealed significant association of / (OR = 4.11, = 0.011) and / -AG (OR = 4.93, = 0.0003) with B-ALL susceptibility. Haplotype analysis of rs4925 and rs156697 revealed that carriers of CG haplotype had increased risk of B-ALL ( = 0.04). Kaplan-Meier plots revealed significantly inferior 3-year disease-free survival for -GG carriers ( = 0.002). Multivariate analysis confirmed -GG as an independent poor prognostic factor for DFS (HR = 4.5, = 0.034). Among combined genotypes, only / -AG associated significantly with poorer DFS rates ( = 0.032). This study demonstrated that individually or in combination with GSTM1 and -AG genotypes associated with increased B-ALL risk. Also, rs156697 variant genotypes (AG and GG) associated with B-ALL, whereas the GG genotype of rs156697 influenced the treatment outcome.