The association of folate pathway and DNA repair polymorphisms with susceptibility to childhood acute lymphoblastic leukemia

• DNA repair and folate pathway polymorphisms may influence ALL susceptibility.
• MTHFR TA and RAD51 GTT haplotypes significantly decreased susceptibility to ALL.
• Susceptibility to ALL increased with the increasing number of risk alleles.
• hOGG–RAD51 and NBN–RAD51 interactions may modify susceptibility to ALL.
• Combination of several polymorphisms may affect susceptibility to childhood ALL.

Genetic factors may play an important role in susceptibility to childhood acute lymphoblastic leukemia (ALL). The aim of our study was to evaluate the associations of genetic polymorphisms in folate pathway and DNA repair genes with susceptibility to ALL. In total, 121 children with ALL and 184 unrelated healthy controls of Slovenian origin were genotyped for 14 polymorphisms in seven genes of folate pathway, base excision repair and homologous recombination repair (TYMS, MTHFR, OGG1, XRCC1, NBN, RAD51, and XRCC3). In addition, the exon 6 of NBN was screened for the presence of mutations using denaturing high performance liquid chromatography. Twelve polymorphisms were in Hardy–Weinberg equilibrium in controls and their genotype frequencies were in agreement with those reported in other Caucasian populations. Among the investigated polymorphisms and mutations, NBN Glu185Gln significantly decreased susceptibility to B-cell ALL (p = 0.037), while TYMS 3R allele decreased susceptibility to T-cell ALL (p = 0.011). Moreover, significantly decreased susceptibility to ALL was observed for MTHFR TA (p = 0.030) and RAD51 GTT haplotypes (p = 0.016). Susceptibility to ALL increased with the increasing number of risk alleles (ptrend = 0.007). We also observed significant influence of hOGG–RAD51 and NBN–RAD51 interactions on susceptibility to ALL. Our results suggest that combination of several polymorphisms in DNA repair and folate pathways may significantly affect susceptibility to childhood ALL.