Association between C3435T Polymorphism of MDR1Gene with Childhood Acute Lymphoblastic Leukaemia and Its Impact on Therapy Response

Main Authors: Ahmed Yakoub, Nashwa MA. Al Azizi, Naglaa A. Khalifa, Mervat Atfy
Format: Article info application/pdf Journal
Bahasa: eng
Terbitan: IJHS Medical Association , 2015
Subjects:
ALL
Online Access: https://www.ijhsonline.com/index.php/IJHS/article/view/200
https://www.ijhsonline.com/index.php/IJHS/article/view/200/129
Daftar Isi:
  • Introduction: Acute lymphoblastic leukemia (ALL) is the major pediatric malig­nancy of all childhood cancers. P glycoprotein (P-gp) is encoded by multidrug resistance 1(MDR1) gene. Many studies have been conducted to investigate possible role of MDR1 C3435T polymorphism with leukemia risk. Methods: Using PCR-RFLP technique, we investigated 100 children (50 cases newly diagnosed with ALL and 50 control subjects) forMDR1 C3435T polymorphism.Results: The homozygous mutant type (T/T) was 32% in ALL patients compared with 12% in controls. It was associated with occurrence of ALL (Odds ratio (OR), 95% confidence interval (CI); 6.1, 1.6-24.6; P=0.002). The mutant heterozygous CT genotype was also more frequently represented among patients 48% compared with 42% in controls. The difference was statistically significant (p =0.04). In addition calculated OR revealed 2.6 fold increased risk of ALL. The wild C/C genotype was associated with worse response to treatment than all mutant genotypes (TT+CT) with p =0.02. Conclusion: MDR1 C3435T polymorphism including CT and TT genotypes are associated with increased risk of childhood acute lymphoblastic leukemia. The CC genotype may be connected to poor response to treatment and poor prognosis.