DNA repair gene XRCC1 polymorphisms in childhood acute lymphoblastic leukemia

Defective DNA repair has been reported to be a risk factor for various malignancies. Genetic polymorphisms of DNA repair genes are thought to result in different phenotypic features compared to the wild type. Genetic polymorphisms in XRCC1 gene could, through alteration of protein structure, lead to defective functioning of DNA Polβ, PARP and LIG3 enzymes resulting in defective DNA repair and increased risk of childhood acute lymphoblastic leukemia (ALL). The role of DNA repair gene XRCC1 in susceptibility to childhood ALL has, however, not been widely studied and no data exists from Indian children. In this pilot study, through the use of PCR and RFLP, further confirmed by DNA sequencing, we have shown an increased risk of ALL among children with XRCC1 codons 194 and 399 variant genotypes. Among the three variants, only the association between codon 399 variant and risk of ALL appeared to be significant. The risk of ALL was higher in males with codons 194 and 399 polymorphisms than in females. However, no relation was found between the presence of these variant genotypes and treatment outcome.