Novel Associations Between METTL3 Gene Polymorphisms and Pediatric Acute Lymphoblastic Leukemia: A Five-Center Case-Control Study

ObjectiveTo reveal the contributing role of METTL3 gene SNPs in pediatric ALL risk.Patients and MethodsA total of 808 pediatric ALL cases and 1,340 cancer-free controls from five hospitals in South China were recruited. A case-control study by genotyping three SNPs in the METTL3 gene was conducted....

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Main Authors: Xiaoping Liu, Libin Huang, Ke Huang, Lihua Yang, Xu Yang, Ailing Luo, Mansi Cai, Xuedong Wu, Xiaodan Liu, Yaping Yan, Jianyun Wen, Yun Cai, Ling Xu, Hua Jiang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.635251/full
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author Xiaoping Liu
Libin Huang
Ke Huang
Lihua Yang
Xu Yang
Ailing Luo
Mansi Cai
Xuedong Wu
Xiaodan Liu
Xiaodan Liu
Yaping Yan
Jianyun Wen
Yun Cai
Ling Xu
Hua Jiang
author_facet Xiaoping Liu
Libin Huang
Ke Huang
Lihua Yang
Xu Yang
Ailing Luo
Mansi Cai
Xuedong Wu
Xiaodan Liu
Xiaodan Liu
Yaping Yan
Jianyun Wen
Yun Cai
Ling Xu
Hua Jiang
author_sort Xiaoping Liu
collection DOAJ
description ObjectiveTo reveal the contributing role of METTL3 gene SNPs in pediatric ALL risk.Patients and MethodsA total of 808 pediatric ALL cases and 1,340 cancer-free controls from five hospitals in South China were recruited. A case-control study by genotyping three SNPs in the METTL3 gene was conducted. Genomic DNA was abstracted from peripheral blood. Three SNPs (rs1263801 C>G, rs1139130 A>G, and rs1061027 A>C) in the METTL3 gene were chosen to be detected by taqman real-time polymerase chain reaction assay.ResultsThat rs1263801 C>G, rs1139130 A>G, and rs1061027 A>C polymorphisms were significantly associated with increased pediatric ALL risk was identified. In stratification analyses, it was discovered that rs1263801 CC, rs1061027 AA, and rs1139130 GG carriers were more likely to develop ALL in subgroups of common B-ALL, MLL gene fusion. Rs1263801 CC and rs10610257 AA carriers were more possible to increase the risk of ALL in subgroups of low hyperdiploid, and all of these three SNPs exhibited a trend toward the risk of ALL. All of these three polymorphisms were associated with the primitive/naïve lymphocytes and MRD in marrow after chemotherapy in ALL children. Rs1263801 CC and rs1139130 AA alleles provided a protective effect on MRD ≥0.01% among CCCG-treated children. As for rs1139130, AA alleles provided a protective effect on MRD in marrow ≥0.01% on 33 days and 12 weeks among CCCG-treated children, but provided a risk effect on MRD in the marrow ≥0.01% among SCCLG-treated children. As for rs1263801 CC and rs1139130 AA, these two alleles provided a protective effect on MRD in the marrow ≥0.01% among CCCG-treated children.ConclusionIn this study, we revealed that METTL3 gene polymorphisms were associated with increased pediatric ALL risk and indicated that METTL3 gene polymorphisms might be a potential biomarker for choosing ALL chemotherapeutics.
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spelling doaj.art-924b47c295a842f3a3db193473a2f24b2022-12-21T22:28:04ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-09-011110.3389/fonc.2021.635251635251Novel Associations Between METTL3 Gene Polymorphisms and Pediatric Acute Lymphoblastic Leukemia: A Five-Center Case-Control StudyXiaoping Liu0Libin Huang1Ke Huang2Lihua Yang3Xu Yang4Ailing Luo5Mansi Cai6Xuedong Wu7Xiaodan Liu8Xiaodan Liu9Yaping Yan10Jianyun Wen11Yun Cai12Ling Xu13Hua Jiang14Department of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaPediatrics Department, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaPediatric Center of Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaDepartment of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaDepartment of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaDepartment of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaDivision of Birth Cohort Study, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaDepartment of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaDepartment of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Pediatrics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaDepartment of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaObjectiveTo reveal the contributing role of METTL3 gene SNPs in pediatric ALL risk.Patients and MethodsA total of 808 pediatric ALL cases and 1,340 cancer-free controls from five hospitals in South China were recruited. A case-control study by genotyping three SNPs in the METTL3 gene was conducted. Genomic DNA was abstracted from peripheral blood. Three SNPs (rs1263801 C>G, rs1139130 A>G, and rs1061027 A>C) in the METTL3 gene were chosen to be detected by taqman real-time polymerase chain reaction assay.ResultsThat rs1263801 C>G, rs1139130 A>G, and rs1061027 A>C polymorphisms were significantly associated with increased pediatric ALL risk was identified. In stratification analyses, it was discovered that rs1263801 CC, rs1061027 AA, and rs1139130 GG carriers were more likely to develop ALL in subgroups of common B-ALL, MLL gene fusion. Rs1263801 CC and rs10610257 AA carriers were more possible to increase the risk of ALL in subgroups of low hyperdiploid, and all of these three SNPs exhibited a trend toward the risk of ALL. All of these three polymorphisms were associated with the primitive/naïve lymphocytes and MRD in marrow after chemotherapy in ALL children. Rs1263801 CC and rs1139130 AA alleles provided a protective effect on MRD ≥0.01% among CCCG-treated children. As for rs1139130, AA alleles provided a protective effect on MRD in marrow ≥0.01% on 33 days and 12 weeks among CCCG-treated children, but provided a risk effect on MRD in the marrow ≥0.01% among SCCLG-treated children. As for rs1263801 CC and rs1139130 AA, these two alleles provided a protective effect on MRD in the marrow ≥0.01% among CCCG-treated children.ConclusionIn this study, we revealed that METTL3 gene polymorphisms were associated with increased pediatric ALL risk and indicated that METTL3 gene polymorphisms might be a potential biomarker for choosing ALL chemotherapeutics.https://www.frontiersin.org/articles/10.3389/fonc.2021.635251/fullmethyltransferase-like 3acute lymphoid leukemiapolymorphismpediatricsusceptibility
spellingShingle Xiaoping Liu
Libin Huang
Ke Huang
Lihua Yang
Xu Yang
Ailing Luo
Mansi Cai
Xuedong Wu
Xiaodan Liu
Xiaodan Liu
Yaping Yan
Jianyun Wen
Yun Cai
Ling Xu
Hua Jiang
Novel Associations Between METTL3 Gene Polymorphisms and Pediatric Acute Lymphoblastic Leukemia: A Five-Center Case-Control Study
Frontiers in Oncology
methyltransferase-like 3
acute lymphoid leukemia
polymorphism
pediatric
susceptibility
title Novel Associations Between METTL3 Gene Polymorphisms and Pediatric Acute Lymphoblastic Leukemia: A Five-Center Case-Control Study
title_full Novel Associations Between METTL3 Gene Polymorphisms and Pediatric Acute Lymphoblastic Leukemia: A Five-Center Case-Control Study
title_fullStr Novel Associations Between METTL3 Gene Polymorphisms and Pediatric Acute Lymphoblastic Leukemia: A Five-Center Case-Control Study
title_full_unstemmed Novel Associations Between METTL3 Gene Polymorphisms and Pediatric Acute Lymphoblastic Leukemia: A Five-Center Case-Control Study
title_short Novel Associations Between METTL3 Gene Polymorphisms and Pediatric Acute Lymphoblastic Leukemia: A Five-Center Case-Control Study
title_sort novel associations between mettl3 gene polymorphisms and pediatric acute lymphoblastic leukemia a five center case control study
topic methyltransferase-like 3
acute lymphoid leukemia
polymorphism
pediatric
susceptibility
url https://www.frontiersin.org/articles/10.3389/fonc.2021.635251/full
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