{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:01:22Z","timestamp":1784541682506,"version":"3.55.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      TANK-binding kinase 1 (TBK1) plays a critical role in driving inflammation and carcinogenesis. We aimed to investigate whether\n                      <jats:italic toggle=\"yes\">TBK1<\/jats:italic>\n                      single nucleotide polymorphisms (SNPs) were associated with the selection of hepatitis B virus (HBV) mutations, and to explore their interaction in modulating the risk of hepatocellular carcinoma (HCC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Four\n                      <jats:italic toggle=\"yes\">TBK1<\/jats:italic>\n                      SNPs (rs12313449, rs73122364, rs7486100, and rs11175413) were genotyped in 3405 participants using quantitative PCR. HBV mutations were determined by Sanger sequencing. Interactions of\n                      <jats:italic toggle=\"yes\">TBK1<\/jats:italic>\n                      polymorphisms and HBV mutations were examined on both additive and multiplicative scales. A dual-luciferase assay was performed to assess the transcriptional activity of fragments containing rs12313449, rs73122364, rs7486100, and rs11175413 polymorphic genotypes. We evaluated the association between\n                      <jats:italic toggle=\"yes\">TBK1<\/jats:italic>\n                      SNPs and HCC prognosis in 397 surgically treated HCC patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Variant genotypes of rs12313449, rs73122364, and rs7486100 were associated with an increased risk of HCC. In genotype C HBV-infected subjects, GA and AA genotypes at rs12313449, AT and TT genotypes at rs73122364, and TA and AA genotypes at rs7486100 were associated with a higher prevalence of HBV mutations including T1753A\/C, A1762T\/G1764A, G1896A, and preS deletion, which increase HCC risk. The interactions of variant genotypes of rs12313449, rs73122364, and rs7486100 with T1753A\/C, A1762T\/G1764A, and G1896A were significantly associated with an increased HCC risk.\n                      <jats:italic toggle=\"yes\">TBK1<\/jats:italic>\n                      promoter with rs12313449-A showed a higher activity than that with rs12313449-G and was more strongly up-regulated by TNF-\u03b1 and IL-6 stimulation. GA and AA genotypes at rs12313449 were associated with worse overall survival and recurrence-free survival and were unfavorable prognostic factors for HCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">TBK1<\/jats:italic>\n                      genetic polymorphisms may facilitate immune selection of HCC-associated HBV mutations and are associated with HCC development, possibly through synergistic interactions with specific HCC-associated HBV mutations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/js9.0000000000005145","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T12:01:24Z","timestamp":1773835284000},"page":"13008-13019","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Effects of TBK1 genetic polymorphisms and their interactions with hepatitis B virus mutations on the risk of hepatocellular carcinoma in Han Chinese population: a case\u2013control study"],"prefix":"10.1097","volume":"112","author":[{"given":"Ge","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Second Affiliated Hospital of Shandong First Medical University, Tai\u2019an, Shandong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyan","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Second Affiliated Hospital of Shandong First Medical University, Tai\u2019an, Shandong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Second Affiliated Hospital of Shandong First Medical University, Tai\u2019an, Shandong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Cai","sequence":"additional","affiliation":[{"name":"School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunning","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Second Affiliated Hospital of Shandong First Medical University, Tai\u2019an, Shandong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Chen","sequence":"additional","affiliation":[{"name":"Interventional Radiology Department, Second Affiliated Hospital of Shandong First Medical University, Tai\u2019an, Shandong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Public Health, Jinan Central Hospital, Jinan, Shandong, 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