Research Paper|Volume 15, Issue 15|pp 7583—7592

TRMT61B rs4563180 G>C variant reduces hepatoblastoma risk: a case-control study of seven medical centers

Dingyuan Zeng¹, Jinhong Zhu², Jingjing Li¹, Fan Liao³, Zhonghua Yang⁴, Yong Li⁵, Jiao Zhang⁶, Jiwen Cheng⁷, Suhong Li⁸, Li Li⁹, Jing He^3,¹⁰

¹Department of Gynecology and Obstetrics, Guangxi Clinical Research Center for Obstetrics and Gynecology, Liuzhou Key Laboratory of Gynecologic Oncology, Liuzhou Hospital, Guangzhou Women and Children’s Medical Center, Liuzhou 545616, Guangxi, China
²Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China
³Department 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 University, Guangzhou 510623, Guangdong, China
⁴Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China
⁵Department of Pediatric Surgery, Hunan Children’s Hospital, Changsha 410004, Hunan, China
⁶Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
⁷Department of Pediatric Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi, China
⁸Department of Pathology, Children Hospital and Women Health Center of Shanxi, Taiyuan 030013, Shannxi, China
⁹Kunming 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 Hospital, Kunming 650228, Yunnan, China
¹⁰Department of Pediatric Surgery, Liuzhou Key Laboratory of Birth Defect Prevention and Control, Liuzhou Hospital, Guangzhou Women and Children’s Medical Center, Liuzhou 545616, Guangxi, China

* Equal contribution

Received: May 15, 2023Accepted: July 19, 2023Published: August 1, 2023

https://doi.org/10.18632/aging.204926

Copyright: © 2023 Zeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

N¹-methyladenosine (m¹A) is an essential chemical modification of RNA. Dysregulation of RNA m¹A modification and m¹A-related regulators is detected in several adult tumors. Whether aberrant RNA m¹A modification is involved in hepatoblast carcinogenesis has not been reported. tRNA methyltransferase 61B (TRMT61B) is responsible for mitochondrial RNA m¹A modification. Some evidence has shown that genetic variants of TRMT61B might contribute to cancer susceptibility; however, its roles in hepatoblastoma are unknown. This study attempted to discover novel hepatoblastoma susceptibility loci. With the TaqMan method, we examined genotypes of the TRMT61B rs4563180 G>C polymorphism among germline DNA samples from 313 cases and 1446 controls. The association of the rs4563180 G>C polymorphism with hepatoblastoma risk was estimated based on odds ratios (ORs) and 95% confidence intervals (CIs). We found that the TRMT61B rs4563180 G>C polymorphism correlated significantly with a reduction in hepatoblastoma risk (GC vs. GG: adjusted OR=0.65, 95% CI=0.49-0.85, P=0.002; GC/CC vs. GG: adjusted OR=0.66, 95% CI=0.51-0.85, P=0.002). In stratified analysis, significant associations were detected in children younger than 17 months old, girls, and subgroups with stage I+II or III+IV tumors. False-positive report probability analysis validated that children with the GC or CC genotype, particularly in those <17 months of age, had a decreased risk of hepatoblastoma. The rs4563180 G>C polymorphism also correlated with expression of TRMT61B and the nearby gene PPP1CB. We identified a high-quality biomarker measuring hepatoblastoma susceptibility, which may contribute to future screening programs.