{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T02:18:06Z","timestamp":1740104286699,"version":"3.37.3"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Signal transducer and activator of transcription 4 (STAT4) is closely related to liver diseases and affects the processes of inflammation and carcinogenesis by regulating immune responses. A single\u2010nucleotide polymorphism rs7574865 (T\u2009&gt;\u2009G) in <jats:italic>STAT4<\/jats:italic> has been reported to be associated with the risk of hepatocellular carcinoma (HCC). In addition, hepatitis B virus (HBV) mutations are crucial risk factors for HBV\u2010induced HCC. However, the effects of the interactions of <jats:italic>STAT4<\/jats:italic> rs7574865 with HBV mutations on the risk of HCC remain unknown. Rs7574865 was genotyped in 846 healthy controls (HCs), 968 chronic hepatitis B (CHB) subjects, 316 liver cirrhosis (LC) subjects and 1021 HCC subjects using Sequenom MassArray. HBV mutations were detected via direct sequencing. Multivariate logistic regression analysis was used to evaluate the effects of the interactions of <jats:italic>STAT4<\/jats:italic> rs7574865 with HBV mutations on the risk of HCC. We found that the rs7574865 TT genotype was significantly associated with HBeAg seroconversion (TT vs. GG, <jats:italic>p<\/jats:italic>\u2009=\u20090.012; TT vs. GT, <jats:italic>p<\/jats:italic>\u2009=\u20090.033). The rs7574865 GG genotype was significantly associated with increased risks of CHB (<jats:italic>p<\/jats:italic>\u2009=\u20090.048), LC (<jats:italic>p<\/jats:italic>\u2009=\u20090.005) and HCC (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). The interaction term between rs7574865 and HBV C1913A significantly increased the risk of progression from CHB to HCC (<jats:italic>p<\/jats:italic>\u2009=\u20090.038), while the interaction term between rs7574865 and HBV T1674C significantly increased the risk of progression from LC to HCC (<jats:italic>p<\/jats:italic>\u2009=\u20090.023).\u00a0<jats:italic>STAT4<\/jats:italic> rs7574865 is significantly associated with the risks of CHB, LC and HCC. The interactions of rs7574865 with HBV C1913A and T1674C mutations significantly increase the risk of HCC, which have the potential to identify HBV\u2010infected individuals who tend to progress from CHB or LC to HCC.<\/jats:p>","DOI":"10.1002\/mc.23449","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T20:23:26Z","timestamp":1658867006000},"page":"933-940","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The effects of the interactions of <i>STAT4<\/i> rs7574865 with HBV mutations on the risk of hepatocellular carcinoma"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0429-6761","authenticated-orcid":false,"given":"Chou","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital Southern Medical University Guangzhou China"},{"name":"The Key Laboratory of Molecular Pathology (Hepatic Diseases) of Guangxi, Department of Pathology The Affiliated Hospital of Youjiang Medical University for Nationalities Baise China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haitao","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital Southern Medical University Guangzhou China"},{"name":"School of Public Health (Shenzhen) Sun Yat\u2010sen University Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Second Military Medical University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8094-1278","authenticated-orcid":false,"given":"Guangwen","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Second Military Medical University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinlin","family":"Hou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deke","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital Southern Medical University Guangzhou China"},{"name":"The Key Laboratory of Molecular Pathology (Hepatic Diseases) of Guangxi, Department of Pathology The Affiliated Hospital of Youjiang Medical University for Nationalities Baise China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8101470"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32723"},{"key":"e_1_2_9_4_1","first-page":"938","article-title":"The guidelines of prevention and treatment for chronic hepatitis B (2019 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STAT4 genetic polymorphism significantly affected HBeAg seroconversion in HBeAg\u2010positive chronic hepatitis B patients receiving Peginterferon\u2010\u03b1 therapy: a prospective cohort study in China.J Med Virol.\u00a0Published online\u00a02022.","DOI":"10.1002\/jmv.27880"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S307962"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26303"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.23449","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mc.23449","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.23449","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T21:13:34Z","timestamp":1692738814000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.23449"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,26]]},"references-count":29,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/mc.23449"],"URL":"https:\/\/doi.org\/10.1002\/mc.23449","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"type":"print","value":"0899-1987"},{"type":"electronic","value":"1098-2744"}],"subject":[],"published":{"date-parts":[[2022,7,26]]},"assertion":[{"value":"2022-01-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}