机构：[1]Henan Provincial Key Laboratory of Children’sGenetics and Metabolic Diseases, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’sHospital, Zhengzhou 450018, Henan, China[2]Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital,Harbin 150040, Heilongjiang, China[3]Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial KeyLaboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou MedicalUniversity, 9 Jinsui Road, Guangzhou 510623, Guangdong, China[4]Kunming Key Laboratory of Children Infection and Immunity, YunnanKey Laboratory of Children’s Major Disease Research, Yunnan Institute of Pediatrics Research, Yunnan Medical Center for Pediatric Diseases,Kunming Children’s Hospital, Kunming 650228, Yunnan, China[5]Department of Pediatric Surgery, The First Affiliated Hospital of ZhengzhouUniversity, Zhengzhou 450052, Henan, China[6]Department of Pediatric Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004, Shaanxi, China[7]Department of Pediatric Surgery, Hunan Children’s Hospital, Changsha 410004, Hunan, China[8]Departmentof Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China中国医科大学附属盛京医院中国医科大学盛京医院[9]Department of Pathology,Children Hospital and Women Health Center of Shanxi, Taiyuan 030013, Shannxi, China[10]Department of Pediatric Oncologic Surgery,Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, 33 Longhu Waihuan EastRoad, Zhengzhou 450018, Henan, China
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.
基金：
Natural Science Foundation of Guangdong Province [2019A1515010360]; Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Diseases [2019B030301004]
