PIWIL1 gene polymorphism and pediatric acute lymphoblastic leukemia relapse susceptibility among Chinese children: a five-center case-control study

Wenjiao Ding; Dao Wang; Mansi Cai; Yaping Yan; Shanshan Liu; Xiaodan Liu; Ailing Luo; Decheng Deng; Xiaoping Liu; Hua Jiang

doi:10.3389/fonc.2023.1203002

PIWIL1 gene polymorphism and pediatric acute lymphoblastic leukemia relapse susceptibility among Chinese children: a five-center case-control study

Front Oncol. 2023 Nov 2:13:1203002. doi: 10.3389/fonc.2023.1203002. eCollection 2023.

Authors

Wenjiao Ding^#¹, Dao Wang^#², Mansi Cai¹, Yaping Yan¹, Shanshan Liu¹, Xiaodan Liu³, Ailing Luo¹, Decheng Deng¹, Xiaoping Liu¹, Hua Jiang¹

Affiliations

¹ Department of Hematology and Oncology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Province Clinical Research Center for Child Health, Guangzhou, Guangdong, China.
² Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³ Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China.

^# Contributed equally.

Abstract

Objective: PIWIL1 polymorphisms' role in pediatric acute lymphoblastic leukemia (ALL) relapse susceptibility remains undiscovered.

Methods: A case-control designed and multiple logistic regression model was performed to evaluate the overall risk of pediatric ALL and five single-nucleotide polymorphisms (SNPs) of PIWIL1 gene (rs35997018 C>T, rs1106042 A>G, rs7957349 C>G, rs10773771 C>T, and rs10848087 A>G) in 785 cases and 1,323 controls, which were genotyped by TaqMan assay. The odds ratio (OR) and its 95% confidence interval (CI) were used to estimate the relationship. Stratified analysis was used to investigate the correlation of rs1106042 and rs10773771 genotypes and pediatric ALL relapse susceptibility in terms of age, sex, number of white blood cells (WBC), immunophenotyping, gene fusion type, karyotype, primitive/naïve lymphocytes, and minimal residual disease (MRD) in bone marrow. Finally, the haplotype analysis was performed to appraise the relationship between inferred haplotypes of PIWIL1 and pediatric ALL risk.

Results: Among the five analyzed SNPs, rs1106042 A>G was related to increased ALL risk, and rs10773771 C>T was related to decreased ALL risk. Compared to the GG genotype, the rs1106042 GA/AA had a deleterious effect on children of age <120 months, who were female and male, had high or average number of WBC, pro-B ALL, pre-B ALL, T-ALL, low- and middle-risk ALL, E2A-PBX fusion gene, non-gene fusion, abnormal diploid, high hyperdiploid, hypodiploid, and normal diploid. Moreover, rs1106042 A>G harmfully affected primitive/naïve lymphocytes and MRD on days 15-19, day 33, and week 12. On the contrary, rs10773771 TC/CC exhibited a protective effect on ALL children with the TEL-AML fusion gene. Haplotype analysis demonstrated that haplotypes CAGT, TACC, TACT, and TAGT were significantly associated with increased pediatric ALL relapse susceptibility.

Conclusion: PIWIL1 rs1106042 A>G was related to increased ALL risk, and rs10773771 C>T was linked to decreased ALL risk in eastern Chinese children. Rs1106042 GA/AA may predict poor prognosis.

Keywords: PIWIL1; acute lymphoblastic leukemia; piRNA; polymorphism; relapse susceptibility.

Grants and funding

This work was supported by grants from the Guangzhou Municipal Science and Technology Project (202201020603 and 202102010262) and the Guangzhou Municipal Clinical Featured Technology Project (2019TS56).