Validations of Top and Novel Susceptibility Variants in All-Age Chinese Patients With Acute Lymphoblastic Leukemia.

Through genome-wide association studies (GWAS), multiple inherited predispositions to acute lymphoblastic leukemia (ALL) have been identified in children. Most recently, a novel susceptibility locus atERGwas localized, exhibiting Hispanic-specific manner. In this study, we conducted a replication study to in all-age Chinese patients (N= 451), not only validating the novelERGlocus, but also systematically determining the impact of age on association status of the top GWAS signals. We found that single nucleotide polymorphisms atARID5B,IKZF1,CEBPE,PIP4K2Awere only significantly associated with ALL susceptibility in childhood patients with noBCR-ABLfusion, whileGATA3signal exhibited its significance in adults no matter carryingBCR-ABLfusion or not. Moreover, the novelERGSNP can be validated in pediatric patients without bothBCR-ABLandETV6-RUNX1fusion. Our finding suggests the modifying effects of age on genetic predisposition to ALL, and highlights the impact ofERGSNP in Chinese patients.