Interaction of thymidylate synthase polymorphism with MTHFR variants modify the risk of childhood acute lymphoblastic leukemia

A genetic susceptibility to acute lymphoblastic leukemia (ALL) has been suggested. The present study was conducted to examine the influence of interaction between methylenetetrahydrofolate reductase (MTHFR) variants and thymidylate synthase (TS) 28base pair (bp) repeat polymorphism on the risk of pediatric ALL. Sixty eight ALL children with the mean age of 8.19±4.0 years and 70 ageand sex-matched healthy children were studied for TS 28-bp repeat and MTHFR C677T and A1298C variants using PCR and PCR-RFLP, respectively. The presence of TS 2R allele had a protective effect on the risk of ALL that did not reach a statistical significance [OR=0.5 (95% CI 0.191.24, p=0.13)]. Also, the effect of MTHFR 677T allele on the risk of ALL was similar to TS 2R allele [OR=0.5 (95% CI 0.181.4, p=0.19)]. However, there was a trend toward increased risk of ALL in the presence of both TS 2R and MTHFR 677T alleles [OR=1.92 (95% CI 0.75.3, p=0.2)]. In contrast, the overall distribution of interaction between TS 2R and MTHFR 1298C alleles in ALL patients compared to controls was not significant. Our results suggest that the interaction between polymorphisms of different genes instead of the one polymorphism in a single gene might determine the susceptibility to pediatric ALL.