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Recently, genome-wide association studies (GWAS) have identified several susceptibility loci for childhood acute lymphoblastic leukemia (ALL) in populations of European descent; only a few loci could be confirmed in Asian populations because of those populations’ genetic heterogeneity. To identify genetic factors associated with childhood ALL risk in the Chinese population, we performed a three-stage GWAS of 1184 childhood ALL cases and 3219 non-ALL controls. The combined analysis identified a new locus (rs1121404 in  WWOX ) at 16q23.1 associated with childhood ALL susceptibility (odds ratio (OR) = 1.38,  P  = 5.29 × 10 −10 ), especially in the subtype of B-ALL (OR = 1.39,  P  = 2.47 × 10 −9 ). The functional studies subsequently revealed that the expression of  WWOX  in ALL bone marrow was significantly lower than that in normal bone marrow. The G allele of rs1121404 displayed significantly decreased levels of mRNA expression of  WWOX . These results suggest that  WWOX  plays an important role in the development of childhood ALL and provide new insights into the etiology of childhood ALL.

Identification of a novel susceptibility locus at 16q23.1 associated with childhood acute lymphoblastic leukemia in Han Chinese