{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T23:38:34Z","timestamp":1775950714533,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017340","name":"Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease","doi-asserted-by":"publisher","award":["2019B030301004"],"award-info":[{"award-number":["2019B030301004"]}],"id":[{"id":"10.13039\/100017340","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatoblastoma, the most frequently diagnosed primary paediatric liver tumour, bears the lowest somatic mutation burden among paediatric neoplasms. Therefore, it is essential to identify pathogenic germline genetic variants, especially those in oncogenic genes, for this disease. The tRNA methyltransferase 6 noncatalytic subunit (TRMT6) forms a tRNA methyltransferase complex with TRMT61A to catalyse adenosine methylation at position N1 of RNAs. TRMT6 has displayed tumour\u2010promoting functions in several cancer types. However, the contribution of its genetic variants to hepatoblastoma remains unclear. In this study, we investigated the association between four <jats:italic>TRMT6<\/jats:italic> polymorphisms (rs236170 A\u2009&gt;\u2009G, rs451571 T\u2009&gt;\u2009C, rs236188 G\u2009&gt;\u2009A and rs236110 C\u2009&gt;\u2009A) and the risk of hepatoblastoma in a cohort of 313 cases and 1446 healthy controls. Germline DNA was subjected to polymorphism genotyping via the TaqMan qPCR method. Odds ratio (OR) and 95% confidence interval (CI) were used to determine hepatoblastoma susceptibility variants. The rs236170 A\u2009&gt;\u2009G, rs236188 G\u2009&gt;\u2009A and rs236110 C\u2009&gt;\u2009A polymorphisms were significantly associated with hepatoblastoma risk. Combination analysis of the four polymorphisms revealed that children bearing 1\u20134 risk genotypes were at significantly enhanced hepatoblastoma risk compared to those without risk genotype (adjusted OR\u2009=\u20091.52, 95% CI\u2009=\u20091.19\u20131.95, <jats:italic>p<\/jats:italic>\u2009=\u20090.0008). We also conducted stratification analyses by age, sex and clinical stage. Ultimately, we found that the rs236110 C\u2009&gt;\u2009A was significantly associated with the downregulation of MCM8, a neighbouring gene of <jats:italic>TRMT6<\/jats:italic>. In conclusion, we identified three susceptibility loci in the <jats:italic>TRMT6<\/jats:italic> gene for hepatoblastoma. Our findings warrant further validation by extensive case\u2013control studies across different ethnicities.<\/jats:p>","DOI":"10.1111\/jcmm.18006","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T06:54:16Z","timestamp":1697612056000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Identification of hepatoblastoma susceptibility loci in the <scp><i>TRMT6<\/i><\/scp> gene from a seven\u2010center case\u2013control study"],"prefix":"10.1111","volume":"28","author":[{"given":"Lin","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory The First Affiliated Hospital of Zhengzhou University, Key Clinical Laboratory of Henan Province  Zhengzhou Henan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0408-3101","authenticated-orcid":false,"given":"Jinhong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Biobank, Harbin Medical University Cancer Hospital  Harbin Heilongjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery the First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenli","family":"Zhang","sequence":"additional","affiliation":[{"name":"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 Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Hunan Children's Hospital  Changsha Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhonghua","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Shengjing Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology Children Hospital and Women Health Center of Shanxi  Taiyuan Shannxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiwen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery the Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"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 Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1954-2892","authenticated-orcid":false,"given":"Jing","family":"He","sequence":"additional","affiliation":[{"name":"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 Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Intensive Care Unit the First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29790-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2022.11.045"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.692130"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-022-00951-1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26718-6"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000046"},{"key":"e_1_2_9_8_1","first-page":"288","article-title":"Recent incidences and trends of childhood malignant solid tumors in Shanghai, 2002\u20102010","volume":"51","author":"Bao PP","year":"2013","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25795"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-022-00545-7"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.76255"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2021.145834"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2020.06.007"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207499"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.3249"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.42798"},{"key":"e_1_2_9_17_1","first-page":"51","article-title":"HMGA2 polymorphisms and Hepatoblastoma susceptibility: a five\u2010center case\u2010control study","volume":"13","author":"Li L","year":"2020","journal-title":"Pharmgenomics Pers Med"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.46120"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33722"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-006-0361-5"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12836"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.21147\/j.issn.1000-9604.2023.02.05"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-022-00562-0"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2020.12.013"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16067-1"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1508054"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw3535"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25480"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(19)30018-5"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.01.002"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-0879-3"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.18006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T09:37:08Z","timestamp":1758533828000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.18006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,18]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1111\/jcmm.18006"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.18006","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,18]]},"assertion":[{"value":"2023-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e18006"}}