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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 <jats:italic>METTL1<\/jats:italic> 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Materials and methods<\/jats:title>\n                <jats:p>Using the TaqMan assay, we genotyped three <jats:italic>METTL1<\/jats:italic> polymorphisms (rs2291617 G\u2009&gt;\u2009T, rs10877013 T\u2009&gt;\u2009C, rs10877012 T\u2009&gt;\u2009G) in germline DNA samples from 1759 Chinese children of Han ethnicity (313 cases vs. 1446 controls).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>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\u2009=\u20091.47, 95% confidence interval\u2009\u20091.07\u20132.02; <jats:italic>P<\/jats:italic>\u2009=\u20090.018). Stratified analyses revealed significant effects of combined polymorphisms mainly among young children (&lt;\u200917 months of age), boys, and those with advanced hepatoblastoma.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>We identified some potential functional <jats:italic>METTL1<\/jats:italic> gene polymorphisms that work together to increase the risk of hepatoblastoma among Chinese Han children; single polymorphism showed only weak effects. These <jats:italic>METTL1<\/jats:italic> 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s12672-022-00545-7","type":"journal-article","created":{"date-parts":[[2022,8,20]],"date-time":"2022-08-20T04:02:32Z","timestamp":1660968152000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["METTL1 gene polymorphisms synergistically confer hepatoblastoma susceptibility"],"prefix":"10.1007","volume":"13","author":[{"given":"Lili","family":"Ge","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiabin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiwen","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhonghua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,8,20]]},"reference":[{"issue":"5","key":"545_CR1","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1002\/pbc.24215","volume":"59","author":"LG Spector","year":"2012","unstructured":"Spector LG, Birch J. 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Written informed consent was acquired from the parents or guardians of each participant. This study was approved by the Institutional Review Board of Guangzhou Women and Children\u2019s Medical Center (No: 202016601).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors have no conflicts of interest to declare.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"77"}}