Affiliation:
1. Department of Hematology/Oncology Guangzhou Women and Children’s Medical Center Guangzhou Medical University Guangzhou China
2. Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangdong Provincial Clinical Research Center for Child Health Guangzhou China
3. Pediatric Center of Zhujiang Hospital Southern Medical University Guangzhou Guangdong China
4. Victoria College University of Toronto Toronto Ontario Canada
5. Division of Birth Cohort Study Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangdong Provincial Clinical Research Center for Child Health Guangzhou Guangdong China
6. Department of Pediatrics Nanfang Hospital Southern Medical University Guangzhou China
7. Department of Pediatrics Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China
Abstract
AbstractBackgroundAcute lymphoblastic leukemia (ALL) is the most common cancer in children. IKZF3 (IKAROS family zinc finger 3) is a hematopoietic‐specific transcription factor, and it has been validated that it is involved in leukemia. However, the role of IKZF3 single‐nucleotide polymorphisms (SNPs) remains unclear. In this case–control study, the authors investigated the association of IKZF3 SNPs with ALL in children.MethodsSix IKZF3 reference SNPs (rs9635726, rs2060941, rs907092, rs12946510, rs1453559, and rs62066988) were genotyped in 692 patients who had ALL (cases) and in 926 controls. The associations between IKZF3 polymorphisms and ALL risk were determined using odds ratios (ORs) and 95% confidence intervals (CIs). The associations of rs9635726 and rs2060941 with the risk of ALL were further estimated by using false‐positive report probability (FPRP) analysis. Functional analysis in silico was performed to evaluate the probability that rs9635726 and rs2060941 might influence the regulation of IKZF3.ResultsThe authors observed that rs9635726C>T (adjusted OR, 1.49; 95% CI, 1.06–2.11; p = .023) and rs2060941G>T (adjusted OR, 1.51; 95% CI, 1.24–1.84; p = .001) were related to and increased risk of ALL in the recessive and dominant models, respectively. Furthermore, the associations of both rs9635726 (FPRP = .177) and rs2060941 (FPRP < .001) with ALL were noteworthy in the FPRP analysis. Functional analysis indicated that rs9635726 and rs2060941 might repress the transcription of IKZF3 by disrupting its binding to MLLT1, TAF1, POLR2A, and/or RAD21.ConclusionsThis study revealed that IKZF3 polymorphisms were associated with increased ALL susceptibility in children and might influence the expression of IKZF3 by disrupting its binding to MLLT1, TAF1, POLR2A, and/or RAD21. IKZF3 polymorphisms were suggested as a biomarker for childhood ALL.