Skibola et al. (2002) also reported that two other polymorphic genes in the folate pathway conferred decreased risk for ALL: the 5′ UTR polymorphism of TYMS and the 1420C→T polymorphism of SHMT1. An association between the 677C→T substitution in MTHFR and hyperdiploidy, a common cytogenetic aberration in childhood ALL, has also been demonstrated (Pui et al, 2004). Here, TYMS is linked to acute lymphoblastic leukemia.