Abstract 2228: Folate-related genes polymorphism and risk of pediatric acute lymphoplastic leukemia

Abstract

Abstract Background: Childhood acute lymphoblastic leukemia (ALL) is the most common malignancy affecting children, constituting about 30% of all cancers among children. It constitutes about 75% of pediatric acute leukemia with peak incidence between ages 3 and 4. The assertion that ALL may have a genetic basis has long been pursued through association studies based on candidate genes as folate metabolism. Polymorphisms in folate pathway genes may influence the susceptibility to acute lymphoblastic leukemia. Increased risk of ALL was observed in reduced folate carrier protein (RFC1) 80GA variant carriers. A 1.4-fold reduction in ALL risk was observed for carriers of the methyl tetrahydrofolate reductase (MTHFR) 677T allele. Objectives: this study was carried out to evaluate the contribution of MTHFR C677T and RFC1 80GA gene polymorphism and susciptability of childhood acute lymphoblastic leukemia. Materials &Methods: DNA was isolated from 200 children, divided into 2 groups, group I included 100 pediatric ALL patients and group II included 100 healthy donors as controls. Genotyping of MTHFR C677T and RFC1 G80A was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using Hinf I and HhaI restriction endonuclease respectively. Results: MTHFR 677T allele carriers were significantly lower in ALL cases (46%) than healthy controls (56%). Reduction in ALL risk was observed for heterozygous (CT) or homozygous (TT) carriers of the MTHFR 677T allele (OR 0.8; 95% CI, 0.9-1.5; P < 0.002). RFC1 80A allelic carriers have an increased susceptibility to ALL. Risk was increased 2.0 times (OR 3.5; 95% CI, 1.5-4.8 ; P .02) for A-allelic carriers. Conclusion: our data suggested that the MTHFR gene variants are associated with decreased ALL rate and risk. the reduced risk associated with the MTHFR C677T polymorphisms may be the result of changed intracellular folate redistribution. the results of our study also supported the suggestion that RFC1 G80A RFC1 G80A single nucleotide polymorphism contributed to increase the susceptibility and the development of pediatric ALL. Citation Format: Nermin Raafat, Amal Gharib, Usama Elsafy, Tamer Hassan. Folate-related genes polymorphism and risk of pediatric acute lymphoplastic leukemia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2228. doi:10.1158/1538-7445.AM2014-2228