METTL1 gene polymorphisms synergistically confer hepatoblastoma susceptibility
Abstract Introduction Hepatoblastoma is a rare but devastating pediatric liver malignancy. Overexpressed methyltransferase-like 1 (METTL1) is a methyltransferase that catalyzes essential N7-methylguanosine (m7G) modification of eukaryotic mRNA. Accumulating evidence has revealed the oncogenic potent...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2022-08-01
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| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-022-00545-7 |
| _version_ | 1798038766307246080 |
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| author | Lili Ge Jinhong Zhu Jiabin Liu Li Li Jiao Zhang Jiwen Cheng Yong Li Zhonghua Yang Suhong Li Jing He Xianwei Zhang |
| author_facet | Lili Ge Jinhong Zhu Jiabin Liu Li Li Jiao Zhang Jiwen Cheng Yong Li Zhonghua Yang Suhong Li Jing He Xianwei Zhang |
| author_sort | Lili Ge |
| collection | DOAJ |
| description | Abstract Introduction Hepatoblastoma is a rare but devastating pediatric liver malignancy. Overexpressed methyltransferase-like 1 (METTL1) is a methyltransferase that catalyzes essential N7-methylguanosine (m7G) modification of eukaryotic mRNA. Accumulating evidence has revealed the oncogenic potential of METTL1. However, whether METTL1 gene polymorphisms confer susceptibility to hepatoblastoma has not been reported. This study aimed to identify causal relationships between genetic variants of this gene and susceptibility to hepatoblastoma. Materials and methods Using the TaqMan assay, we genotyped three METTL1 polymorphisms (rs2291617 G > T, rs10877013 T > C, rs10877012 T > G) in germline DNA samples from 1759 Chinese children of Han ethnicity (313 cases vs. 1446 controls). Results None of these polymorphisms were associated with hepatoblastoma risk. However, combination analysis showed that children with 1 to 3 risk genotypes were associated with increased hepatoblastoma risk (adjusted odds ratio = 1.47, 95% confidence interval 1.07–2.02; P = 0.018). Stratified analyses revealed significant effects of combined polymorphisms mainly among young children (< 17 months of age), boys, and those with advanced hepatoblastoma. Conclusion We identified some potential functional METTL1 gene polymorphisms that work together to increase the risk of hepatoblastoma among Chinese Han children; single polymorphism showed only weak effects. These METTL1 polymorphisms may be promising biomarkers for screening high-risk individuals for hepatoblastoma. These findings are inspiring and deserve to be validated among individuals of different ethnicities. Graphical Abstract |
| first_indexed | 2024-04-11T21:44:45Z |
| format | Article |
| id | doaj.art-5420d57aca9a4f0f8eec985fe07e457e |
| institution | Directory Open Access Journal |
| issn | 2730-6011 |
| language | English |
| last_indexed | 2024-04-11T21:44:45Z |
| publishDate | 2022-08-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj.art-5420d57aca9a4f0f8eec985fe07e457e2022-12-22T04:01:27ZengSpringerDiscover Oncology2730-60112022-08-011311910.1007/s12672-022-00545-7METTL1 gene polymorphisms synergistically confer hepatoblastoma susceptibilityLili Ge0Jinhong Zhu1Jiabin Liu2Li Li3Jiao Zhang4Jiwen Cheng5Yong Li6Zhonghua Yang7Suhong Li8Jing He9Xianwei Zhang10Henan Provincial Key Laboratory of Children’s Genetics and Metabolic Diseases, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s HospitalDepartment of Clinical Laboratory, Biobank, Harbin Medical University Cancer HospitalDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityKunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children’s Major Disease Research, Yunnan Institute of Pediatrics Research, Yunnan Medical Center for Pediatric Diseases, Kunming Children’s HospitalDepartment of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Pediatric Surgery, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Pediatric Surgery, Hunan Children’s HospitalDepartment of Pediatric Surgery, Shengjing Hospital of China Medical UniversityDepartment of Pathology, Children Hospital and Women Health Center of ShanxiDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Pediatric Oncologic Surgery, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s HospitalAbstract Introduction Hepatoblastoma is a rare but devastating pediatric liver malignancy. Overexpressed methyltransferase-like 1 (METTL1) is a methyltransferase that catalyzes essential N7-methylguanosine (m7G) modification of eukaryotic mRNA. Accumulating evidence has revealed the oncogenic potential of METTL1. However, whether METTL1 gene polymorphisms confer susceptibility to hepatoblastoma has not been reported. This study aimed to identify causal relationships between genetic variants of this gene and susceptibility to hepatoblastoma. Materials and methods Using the TaqMan assay, we genotyped three METTL1 polymorphisms (rs2291617 G > T, rs10877013 T > C, rs10877012 T > G) in germline DNA samples from 1759 Chinese children of Han ethnicity (313 cases vs. 1446 controls). Results None of these polymorphisms were associated with hepatoblastoma risk. However, combination analysis showed that children with 1 to 3 risk genotypes were associated with increased hepatoblastoma risk (adjusted odds ratio = 1.47, 95% confidence interval 1.07–2.02; P = 0.018). Stratified analyses revealed significant effects of combined polymorphisms mainly among young children (< 17 months of age), boys, and those with advanced hepatoblastoma. Conclusion We identified some potential functional METTL1 gene polymorphisms that work together to increase the risk of hepatoblastoma among Chinese Han children; single polymorphism showed only weak effects. These METTL1 polymorphisms may be promising biomarkers for screening high-risk individuals for hepatoblastoma. These findings are inspiring and deserve to be validated among individuals of different ethnicities. Graphical Abstracthttps://doi.org/10.1007/s12672-022-00545-7HepatoblastomaSusceptibilityMETTL1Polymorphismm7G modification |
| spellingShingle | Lili Ge Jinhong Zhu Jiabin Liu Li Li Jiao Zhang Jiwen Cheng Yong Li Zhonghua Yang Suhong Li Jing He Xianwei Zhang METTL1 gene polymorphisms synergistically confer hepatoblastoma susceptibility Discover Oncology Hepatoblastoma Susceptibility METTL1 Polymorphism m7G modification |
| title | METTL1 gene polymorphisms synergistically confer hepatoblastoma susceptibility |
| title_full | METTL1 gene polymorphisms synergistically confer hepatoblastoma susceptibility |
| title_fullStr | METTL1 gene polymorphisms synergistically confer hepatoblastoma susceptibility |
| title_full_unstemmed | METTL1 gene polymorphisms synergistically confer hepatoblastoma susceptibility |
| title_short | METTL1 gene polymorphisms synergistically confer hepatoblastoma susceptibility |
| title_sort | mettl1 gene polymorphisms synergistically confer hepatoblastoma susceptibility |
| topic | Hepatoblastoma Susceptibility METTL1 Polymorphism m7G modification |
| url | https://doi.org/10.1007/s12672-022-00545-7 |
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