Significant association of XRCC4 single nucleotide polymorphisms with childhood leukemia in Taiwan

The DNA repair gene XRCC4, a member of the protein family involved in non-homologous end-joining repair pathway, plays a major role in repairing DNA double-strand breaks. XRCC4 is important in maintaining the overall genome stability, and it is also thought to play a key role in human carcinogenesis. We investigated some novel polymorphic variants of XRCC4, including C-1622T (rs7727691), G-1394T (rs6869366), G-652T (rs2075685), C-571T (rs2075686), intron3 DIP (rs28360071), S247A (rs3734091) and intron7 DIP (rs28360317), and analyzed the association of specific genotype with susceptibility to childhood leukemia.

In total, 266 children with leukemia and 266 age-matched healthy controls recruited from the China Medical Hospital in Central Taiwan were genotyped investigating the association of these polymorphisms with childhood leukemia.

We found differences in frequency of the XRCC4 G-1394T and intron 3 genotype, but not the XRCC4 codon 247, or intron 7, between the childhood leukemia and control groups. Our data indicated the G allele of G-1394T and deletion of intron 3 are clear risk factors of susceptibility to childhood leukemia (p=0.0022 and 0.0075). As for XRCC4 C-1622T and C-571T, there was no difference in the distribution between the two groups. The analysis of joint effect for XRCC4 G-1394T and intron 3 showed that individuals with GT at G-1394T and DD at intron 3 present the highest potential for developing childhood leukemia than other groups (odds ratio=4.94, 95% confidence interval=1.01-24.27, p=0.0404).

Our findings suggest that the G allele of XRCC4 G-1394T and deletion of intron 3 may be responsible for childhood leukemia and may be useful in early detection of child leukemia.