{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:04:25Z","timestamp":1790107465626,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T00:00:00Z","timestamp":1495670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T00:00:00Z","timestamp":1495670400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,1,2]],"date-time":"2017-01-02T00:00:00Z","timestamp":1483315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["kjms-online.com","clinicalkey.jp","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>This case\u2013control study was aimed to assess the effect of genetic variants of <jats:italic>tumor necrosis factor (TNF)<\/jats:italic> \u03b1\u2212308 and <jats:italic>lymphotoxin (LT)<\/jats:italic> \u03b1+252 on development of hepatitis B virus (HBV)\u2010related hepatocellular carcinoma (HCC). Their gene\u2013gene interaction was also investigated. We enrolled 200 pairs of age\u2010 and sex\u2010matched patients with cirrhotic HBV\u2010HCC and unrelated patients with HBV\u2010cirrhosis alone. Polymorphisms of <jats:italic>TNF\u03b1<\/jats:italic>\u2212308 and <jats:italic>LT\u03b1<\/jats:italic>+252 were genotyped. Synergy index was used to calculate interaction between the variant genotypes. The results indicated that the frequency distribution of the variant genotypes (<jats:italic>TNF\u03b1<\/jats:italic>\u2212308 G\/A and <jats:italic>LT\u03b1<\/jats:italic>+252 G\/G) in patients with HCC were significantly higher than those in patients with cirrhosis alone. Multivariate analysis indicated that <jats:italic>TNF\u03b1<\/jats:italic>\u2212308 G\/A (odds ratio [OR], 2.34) and <jats:italic>LT\u03b1<\/jats:italic>+252 G\/G (OR, 2.04) were independent risk factors for HCC. By the clinical characteristics of study population, multivariate analysis demonstrated that independent factors associated with harboring the variant genotypes included cirrhosis with Child\u2010Pugh C (OR\u2009=\u20096.47 in cases and OR\u2009=\u200911.56 in controls) and thrombocytopenia (OR\u2009=\u20098.86 in cases and OR\u2009=\u20097.74 in controls). Calculation of synergy index (SI) indicated that there are additive interaction between <jats:italic>TNF\u03b1<\/jats:italic>\u2212308 G\/A and <jats:italic>LT\u03b1<\/jats:italic>+252 G\/G on risk of HCC (SI\u2009=\u20091.29). In conclusion: There are independent and additive interactions between <jats:italic>TNF\u03b1<\/jats:italic>\u2212308 G\/A and <jats:italic>LT\u03b1<\/jats:italic>+252 G\/G on risk for HBV\u2010HCC. They correlated with advanced hepatic fibrosis and severe liver damage, which might contribute to a higher risk for HCC.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.kjms.2017.04.009","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T16:31:31Z","timestamp":1495729891000},"page":"453-457","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Independent and additive interaction between polymorphisms of <i>tumor necrosis factor \u03b1<\/i>\u2212308 and <i>lymphotoxin \u03b1<\/i>+252 on risk of hepatocellular carcinoma related to hepatitis 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