ABSTRACT
Acute lymphoblastic leukemia (ALL) is the most common form of malignancy in children. Recently, many studies have examined factors influencing both the susceptibility to ALL and the metabolism of widely used chemotherapeutic agents. These factors include, among others, single-nucleotide polymorphisms in various genes, such as the gene encoding for methylenetetrahydrofolate reductase (MTHFR), which has been proven polymorphic at the nucleotide positions 677 and 1298. Thirty-five children with ALL and 48 healthy adults of Cretan origin were genotyped for the presence of the MTHFR 677 and 1298 single-nucleotide polymorphisms. The possible correlation of the polymorphisms with the risk for ALL and the presence of methotrexate-induced toxicities were examined. No significant association between the MTHFR genotypes and the susceptibility to ALL was observed. A borderline statistically significant relationship was detected after methotrexate administration, between the C677T genotype (polymorphisms) and leukopenia (p = 0.050) and between the A1298C polymorphism and normal aspartate transaminase and alanine transaminase values (p = 0.065 and p = 0.053, respectively), which was strengthened for aspartate transaminase, after grouping the A1298A and A1298C genotypes together (p = 0.039). In our population the MTHFR C677T and A1298C polymorphisms are related with hematologic toxicity and hepatotoxicity, respectively, and could be suggested as prognostic factors for these adverse events.
Subject(s)
Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Genetic , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Case-Control Studies , Child , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Greece , Humans , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/enzymologyABSTRACT
Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children. Inherited predisposition and exposure to exogenous leukemogenic agents have been investigated as potential risk factors. Current therapy results in 5-year event-free survival exceeding 80% in children in developed countries. Predisposition to ALL and event-free outcome seems to be influenced by polymorphisms on genes involved in several metabolic pathways. The purpose of this review is to discuss the findings of different studies upon the role of gene polymorphisms in childhood ALL.
