Genetic Variants in METTL14 are Associated with the Risk of Acute Lymphoblastic Leukemia in Southern Chinese Children: A Five-Center Case-Control Study

• Published in: Cancer management and research Vol. 13; pp. 9189 - 9200
• Main Authors: Luo, Ailing, Yang, Lihua, Li, Ming, Cai, Mansi, Huang, Amin, Liu, Xiaodan, Yang, Xu, Yan, Yaping, Wang, Xueliang, Wu, Xuedong, Huang, Ke, Huang, Libin, Liu, Shanshan, Xu, Ling, Liu, Xiaoping
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2021; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Acute lymphocytic leukemia; Age; all; Cancer; Chemotherapy; Children & youth; chinese children; Development and progression; Ethylenediaminetetraacetic acid; Genes; Genetic aspects; Genotype & phenotype; Haplotypes; Leukemia; Lymphocytes; mettl14; Oncology, Experimental; Original Research; Pathogenesis; Pediatrics; Regression analysis; Risk factors; Single nucleotide polymorphisms; snp; susceptibility; China; Beijing China; United States > US; ALL; METTL14; susceptibility; Chinese children; SNP
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S335925

Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer. , an N -methyladenosine (m A) modification protein, plays several roles in cancer development and is involved in the pathogenesis of various types of cancers. However, the role of gene single nucleotide polymorphisms (SNPs) in pediatric ALL susceptibility remains to be investigated. A case-control design and multinomial logistic regression were used to develop models to estimate the overall risk for pediatric ALL and three gene SNPs (rs298982 G/A, rs298981 A/G and rs1064034 T/A) in 808 cases and 1340 controls, which were genotyped using a TaqMan assay. The associations were estimated by odds ratios (ORs) with their 95% confidence intervals (CIs). Furthermore, stratified analysis was performed to explore associations of rs298982 and rs1064034 with pediatric ALL susceptibility in terms of age, sex, immunophenotype, minimal residual disease (MRD), and other clinical characteristics. Among the three analyzed SNPs, rs298982 G/A and rs1064034 T/A exhibited a significant association with decreased childhood ALL risk, while rs298981 A/G exhibited no difference. In stratified analysis, rs298982 GA/AA and rs1064034 TA/AA had a protective effect in children <120 months of age and males, common B ALL, TEL-AML, non gene fusion, normal diploid, and high WBC. However, the rs1064034 TA/AA genotype was associated with an increased risk of mixed immunophenotyping. Compared with the reference haplotype GAT, haplotypes CAA, CGT and CGA were significantly associated with elevated ALL risk, while haplotype GGT was significantly associated decreased ALL risk. Moreover, subjects carrying rs298982 A or rs1064034 A exhibited less minimal MRD after induced chemotherapy. Functional annotations revealed that gene SNPs rs298982 G/A and rs1064034 T/A could be potential functional variants. In conclusion, gene polymorphisms influence the risk of ALL in southern Chinese children and might be potential biomarkers for pediatric ALL susceptibility and chemotherapeutics.