Impact of NQO1, GSTM1 and GSTT1 genetic variants on susceptibility and relapse in childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is a multifactorial malignancy influenced by genetic and environmental factors. Polymorphisms in detoxification enzymes such as NQO1, GSTM1, and GSTT1 may modulate susceptibility and treatment response. This case-control study evaluated 74 children with ALL and 115 cancer-free controls from southern Brazil. Genomic DNA was analyzed for NQO1 rs1800566 (C609T) by PCR-RFLP and for GSTM1 and GSTT1 by multiplex PCR. Plasma glutathione (GSH) levels were measured spectrophotometrically. Genotype distributions were consistent with Hardy-Weinberg equilibrium. No significant associations were observed between NQO1 rs1800566, GSTM1, or GSTT1 polymorphisms and ALL susceptibility (CT genotype OR = 0.88, 95 % CI = 0.46-1.72, p = 0.74; GSTM1 null OR = 0.70; GSTT1 null OR = 1.12). However, the NQO1 T allele was linked to a lower relapse rate (p = 0.03), suggesting a potential protective role. Mean plasma GSH levels were higher in ALL patients (17.41 nmol/L) than in controls (12.16 nmol/L), though unrelated to genotype or outcome. Overall, NQO1, GSTM1, and GSTT1 variants were not associated with ALL risk, but the NQO1 rs1800566 polymorphism may influence relapse, possibly via altered quinone metabolism. Larger multiethnic studies integrating genetic and pharmacogenomic data are warranted to clarify their role in ALL pathogenesis.