METTL1 gene polymorphisms synergistically confer hepatoblastoma susceptibility

作者：Lili Ge, Jinhong Zhu, Jiabin Liu, Li Li, Jiao Zhang, Jiwen Cheng, Yong Li, Zhonghua Yang, Suhong Li, Jing He, Xianwei Zhang · 发表于：Discover Oncology · 年份：2022 · DOI：10.1007/s12672-022-00545-7 · 被引用次数：8 · 研究领域：RNA modifications and cancer、Acute Lymphoblastic Leukemia research、Viral-associated cancers and disorders

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 f...