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
- 1 Department 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
- 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 Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
- 4 Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China
- 5 Department of Pediatric Surgery, Hunan Children’s Hospital, Changsha 410004, Hunan, China
- 6 Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
- 7 Department of Pediatric Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi, China
- 8 Department of Pathology, Children Hospital and Women Health Center of Shanxi, Taiyuan 030013, Shannxi, China
- 9 Kunming 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
- 10 Department 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
Received: May 15, 2023 Accepted: July 19, 2023 Published: August 1, 2023
https://doi.org/10.18632/aging.204926How to Cite
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.
Abbreviations
BWS: Beckwith–Wiedemann syndrome; XPC: xeroderma pigmentosum, complementation group C; METTL14: methyltransferase like 14; HMGA2: high mobility group AT-hook 2; WDR4: WD repeat domain 4; YTHDF1: YTH N6-methyladenosine RNA-binding protein F1; WTAP: WT1-associated protein; m1A: N1-methyladenosine; lncRNA: long noncoding RNA; TRMT6: tRNA methyltransferase 6; HCC: hepatocellular carcinoma; SNP: single-nucleotide polymorphism; OR: odds ratio; CI: confidence interval; FPRP: false-positive report probability; eQTL: expression quantitative trait locus; PPP1CB: protein phosphatase 1 catalytic subunit beta; ALKBH5: AlkB homolog 5; PP1: protein phosphatase 1; TFBS: transcription factor-binding site; GTEx: Genotype-Tissue Expression; HWE: Hardy-Weinberg equilibrium.