Genetic susceptibility of IKZF1, ARID5B, and CEBPE polymorphisms to childhood acute lymphoblastic leukemia in Chinese populations: a case-control study

Abstract

Objective This study aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in IKZF1, ARID5B, and CEBPE with acute lymphoblastic leukemia (ALL) susceptibility in Chinese children.

Methods A case-control study was conducted involving 360 ALL patients and 398 healthy controls. Nine SNPs were genotyped, and their associations with ALL risk were analyzed using logistic regression under various genetic models. Multifactor dimensionality reduction (MDR) analysis was employed to investigate SNP-SNP interactions.

Results Seven of the nine SNPs were significantly associated with ALL susceptibility. Specifically, IKZF1 SNPs (rs11980379, rs4132601, rs10272724) and a CEBPE SNP (rs4982731) were associated with an increased risk of ALL. In contrast, ARID5B SNPs (rs10994982, rs10821938) and another CEBPE SNP (rs2144827) were associated with a reduced risk. Stratified analyses revealed age- and sex-specific associations. MDR analysis identified significant SNP-SNP interactions, with a robust four-SNP model (rs10994982, rs2144827, rs10272724, rs10821938) showing the best predictive performance for ALL risk.

Conclusion Specific SNPs in IKZF1, ARID5B, CEBPE and their interactions are associated with childhood ALL susceptibility in Chinese populations, providing references for ALL risk stratification.

Keywords

Acute lymphoblastic leukemia / Single nucleotide polymorphism / SNP-SNP interaction

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declaration of Competing Interest

The authors declare no conflicts of interest.

Acknowledgments

This work was supported by General Program of the Xuzhou Key Research and Development Program (KC22201),Jiangsu Provincial Medical Key Discipline Cultivation Unit (JSDW202239), Nanjing Medical Key Laboratory of Laboratory Medicine.

Author contributions

Each author has contributed to the relevant work of this study. X.C., Y.W. designed the main study, analyzed the data and drafted the article. Y.K., U.A. checked all the analyses and refined the article. Y.Y. provided much help in samples collection and analysis. D.F. and B.H. decided the main direction of the study and made the final revision of the article. All authors read and app roved the final version of the article.

Ethics Statement

This study has obtained informed consent from all participants and the ethics committee of Xuzhou Children’s Hospital reviewed and approved the research protocol (Ethics No. 2023-05-09-H09).

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