Cancer Management and Research (Dec 2021)

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

  • Luo A,
  • Yang L,
  • Li M,
  • Cai M,
  • Huang A,
  • Liu X,
  • Yang X,
  • Yan Y,
  • Wang X,
  • Wu X,
  • Huang K,
  • Huang L,
  • Liu S,
  • Xu L,
  • Liu X

Journal volume & issue
Vol. Volume 13
pp. 9189 – 9200

Abstract

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Ailing Luo,1,* Lihua Yang,2,* Ming Li,3 Mansi Cai,1 Amin Huang,4 Xiaodan Liu,5 Xu Yang,1 Yaping Yan,1 Xueliang Wang,1 Xuedong Wu,6 Ke Huang,7 Libin Huang,8 Shanshan Liu,1 Ling Xu,1 Xiaoping Liu1 1Department of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Pediatric Center of Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3The Emergency Department of Zhuzhou Central Hospital, Zhuzhou, Hunan, People’s Republic of China; 4Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 5Division of Birth Cohort Study, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 6Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 7Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 8Pediatrics Department, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoping Liu; Ling XuDepartment of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, No. 9, Jinsui Road, Tianhe District, Guangzhou, 510623, Guangdong, People’s Republic of ChinaTel +86-13822283646; +86-13798111250Fax +86-2038076069; +86-2038076557Email [email protected]; [email protected]/Aim: Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer. METTL14, an N6-methyladenosine (m6A) modification protein, plays several roles in cancer development and is involved in the pathogenesis of various types of cancers. However, the role of METTL14 gene single nucleotide polymorphisms (SNPs) in pediatric ALL susceptibility remains to be investigated.Methods: A case-control design and multinomial logistic regression were used to develop models to estimate the overall risk for pediatric ALL and three METTL14 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.Results: 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 METTL14 gene SNPs rs298982 G/A and rs1064034 T/A could be potential functional variants.Conclusion: In conclusion, METTL14 gene polymorphisms influence the risk of ALL in southern Chinese children and might be potential biomarkers for pediatric ALL susceptibility and chemotherapeutics.Keywords: ALL, METTL14, SNP, susceptibility, Chinese children

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