In this issue of Blood, Qian and colleagues ¹ add ERG variants to a growing list of common host DNA polymorphisms that have been associated with an increased risk of childhood acute lymphoblastic leukemia (ALL). It has long been known that Hispanics more frequently develop childhood ALL. In addition to GATA3, PIP4K2A, and ARID5B, this increased risk is now also accounted for by ERG variants with the frequency of risk variants being positively related to the proportion of Native American Ancestry.