The role of MDR1 (C3435T) gene polymorphism in Egyptian acute lymphoblastic leukemia

Abstract

P-glycoprotein (P-gp), a membrane transporter encoded by multidrug resistance 1 (MDR1) gene, influences pharmacokinetics of anticancer drugs and contributes to multidrug resistance phenotype in acute lymphoblastic leukemia (ALL). The MDR1 (C3435T) gene polymorphism is associated with the altered expression and function of P-gp. In this study, we investigated the influence of inherited MDR1 (C3435T) gene polymorphism on the susceptibility to ALL in Egypt in 60 ALL patients (30 childhood and 30 adulthood), together with 60 healthy controls using a polymerase chain reaction–restriction fragment length polymorphism assay. The mutant homozygous T/T genotype was significantly associated with the occurrence of ALL (p = 0.02; odds ratio, 8.000 (95 % confidence interval (CI), 1.425–44.920) in childhood ALL and (p = 0.04; odds ratio, 5.455 (95 % CI, 0.937–31.746) in adulthood ALL patients. The heterozygous C/T genotype was near statistical significance in both childhood and adulthood ALL patients in comparison to controls (p = 0.06). The C/C genotype was associated with worse response to treatment than the mutant type (T/T and C/T; p = 0.009, 0.04) in childhood and adulthood ALL, respectively. These results suggest that the MDR1 T/T genotype might influence risk of development of ALL and the C/C genotype might be linked to a poor prognosis of ALL.