Although LIG4 interacts with the coiled-coil region of human XRCC4 via the region that lies between the two C-terminal BRCT domains[15,20,21], the combined analysis of multiple SNPs revealed that LIG4 rs1805388 which causes a nonsynonymous amino acid change at the N-terminal of the LIG4 protein and XRCC4 rs1805377 interacted to modulate the risk of gliomas as a joint effect. Here, LIG4 is linked to central nervous system cancer.