{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:49:10Z","timestamp":1790113750294,"version":"4.0.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T00:00:00Z","timestamp":1390780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["81072321"],"award-info":[{"award-number":["81072321"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["30960021"],"award-info":[{"award-number":["30960021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["30460143"],"award-info":[{"award-number":["30460143"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["30560133"],"award-info":[{"award-number":["30560133"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"New Century Excellent Talents in University"},{"name":"Guangxi Nature Sciences","award":["0236030"],"award-info":[{"award-number":["0236030"]}]},{"name":"Guangxi Nature Sciences","award":["0632007-1E"],"award-info":[{"award-number":["0632007-1E"]}]},{"name":"Guangxi Nature Sciences","award":["0640101"],"award-info":[{"award-number":["0640101"]}]},{"name":"Guangxi Nature Sciences","award":["0592007-1A"],"award-info":[{"award-number":["0592007-1A"]}]},{"name":"Guangxi Health Ministry Medicine","award":["Z2010108"],"award-info":[{"award-number":["Z2010108"]}]},{"DOI":"10.13039\/100000002","name":"USA National Institutes of Health","doi-asserted-by":"crossref","award":["ES05116"],"award-info":[{"award-number":["ES05116"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"USA National Institutes of Health","doi-asserted-by":"crossref","award":["ES09089"],"award-info":[{"award-number":["ES09089"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,3]]},"abstract":"Abstract<\/jats:title>Background & Aims<\/jats:title>p53 is one of the most frequently mutated human tumour suppressor genes. Chronic infection with hepatitis B virus (HBV<\/jats:styled-content>) and exposure to aflatoxin B1 (AFB<\/jats:styled-content>1) induces p53 mutations in hepatocellular carcinoma (HCC<\/jats:styled-content>) tissue. The aims of present study are to investigate the p53 mutation spectrum in HBV<\/jats:styled-content>\u2010 and AFB<\/jats:styled-content>1\u2010related hepatocarcinogenesis in patients with hepatocellular carcinoma (HCC<\/jats:styled-content>) in Guangxi, China.<\/jats:p><\/jats:sec>Methods<\/jats:title>Tumour and adjacent liver tissue were collected from 397 HCC<\/jats:styled-content> patients who were subdivided into HBV<\/jats:styled-content>(+)\/AFB<\/jats:styled-content>1(+), HBV<\/jats:styled-content>(+)\/AFB<\/jats:styled-content>1(\u2212), HBV<\/jats:styled-content>(\u2212)\/AFB<\/jats:styled-content>1(+) and HBV<\/jats:styled-content>(\u2212)\/AFB<\/jats:styled-content>1(\u2212) four groups. All 11 exons of the p53 gene were PCR<\/jats:styled-content>\u2010amplified and sequenced. Immunohistochemistry was used to evaluate the effect of mutations on the expression of p53 protein.<\/jats:p><\/jats:sec>Results and Conclusions<\/jats:title>P53 mutations were detected in 223 HCC<\/jats:styled-content> samples, 13 adjacent liver tissue samples and only 1 of 68 normal liver tissue samples. The mutation sites concentrated at exon 4, 5, 6, 7, 8, 9 and no mutation was detected in exon 1, 2, 3, 10 and 11. The most frequently occurring mutation was in codon 249 (R249S) in exon 7. Patients in the HBV<\/jats:styled-content>(+)\/AFB<\/jats:styled-content>1(+) and HBV<\/jats:styled-content>(\u2212)\/AFB<\/jats:styled-content>1(+) groups had significantly higher mutation rates compared with patients in the HBV<\/jats:styled-content>(+)\/AFB<\/jats:styled-content>1(\u2212) and HBV<\/jats:styled-content>(\u2212)\/AFB<\/jats:styled-content>1(\u2212) groups. P53 mutation status and HBV<\/jats:styled-content>\/AFB<\/jats:styled-content>1 status were independent predictors of tumour recurrence after surgery. Immunohistochemical analysis revealed that p53 gene mutations were correlated with the p53 expression. In Guangxi area, the significant association between AFB<\/jats:styled-content>1\u2010induced p53 mutations and the expression of p53 protein suggest an important role for p53 mutations in carcinogenesis of HCC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12460","type":"journal-article","created":{"date-parts":[[2014,1,2]],"date-time":"2014-01-02T18:10:12Z","timestamp":1388686212000},"page":"999-1009","source":"Crossref","is-referenced-by-count":74,"title":["The p53 mutation spectrum in hepatocellular carcinoma from Guangxi, China : role of chronic hepatitis B virus infection and aflatoxin B1 exposure"],"prefix":"10.1111","volume":"35","author":[{"given":"Lu\u2010Nan","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery Tumor Hospital of Guangxi Medical University Nanning Guangxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Tumor Hospital of Guangxi Medical University Nanning Guangxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zu\u2010Shun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Tumor Hospital of Guangxi Medical University Nanning Guangxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei\u2010Xiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Tumor Hospital of Guangxi Medical University Nanning Guangxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan\u2010Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ultrasound First Affiliated Hospital of Guangxi Medical University Nanning Guangxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang\u2010","family":"De Xiang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Tumor Hospital of Guangxi Medical University Nanning Guangxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery First Affiliated Hospital of Guangxi Medical University Nanning Guangxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze\u2010Guang","family":"Han","sequence":"additional","affiliation":[{"name":"China National Human Genome Center at Shanghai Shanghai Shanghai City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le\u2010Qun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Tumor Hospital of Guangxi Medical University Nanning Guangxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.04.061"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10175"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10171"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-200x.2004.01867.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1007117"},{"key":"e_1_2_7_7_1","first-page":"51","article-title":"Molecular and genetic epidemiology of hepatocellular carcinoma: studies in China and Senegal","volume":"25","author":"London WT","year":"1995","journal-title":"Princess Takamatsu Symp"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.1997.tb00513.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.0901388"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2013.1169"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.01.006"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/22.4.535"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2004.09.020"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2003.00869.x"},{"key":"e_1_2_7_15_1","first-page":"2506","article-title":"Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China","volume":"49","author":"Yeh FS","year":"1989","journal-title":"Cancer Res"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1905840"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10181"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10176"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.18.8586"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2008.01.012"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2009.02.057"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.06.002"},{"key":"e_1_2_7_23_1","first-page":"3220","article-title":"p53 Mutations in human hepatocellular carcinomas from Germany","volume":"52","author":"Kress S","year":"1992","journal-title":"Cancer Res"},{"key":"e_1_2_7_24_1","first-page":"6358","article-title":"p53 gene mutation spectrum in hepatocellular carcinoma","volume":"52","author":"Oda T","year":"1992","journal-title":"Cancer Res"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12029-010-9140-5"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02572.x"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2012.11.012"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.032482-0"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2008.01.022"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1007122"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(20000401)88:7<1565::AID-CNCR10>3.0.CO;2-9"},{"key":"e_1_2_7_32_1","first-page":"617","article-title":"Hepatitis B, aflatoxin B(1), and p53 codon 249 mutation in hepatocellular carcinomas from Guangxi, People's Republic of China, and a meta\u2010analysis of existing studies","volume":"10","author":"Stern MC","year":"2001","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2723"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2693"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990315)80:6<875::AID-IJC13>3.0.CO;2-Z"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.25545"},{"key":"e_1_2_7_37_1","first-page":"1635","article-title":"p53 mutations cluster at codon 249 in hepatitis B virus\u2010positive hepatocellular carcinomas from China","volume":"52","author":"Scorsone KA","year":"1992","journal-title":"Cancer Res"},{"key":"e_1_2_7_38_1","first-page":"3471","article-title":"p53 mutations, chronic hepatitis B virus infection, and aflatoxin exposure in hepatocellular carcinoma in Taiwan","volume":"57","author":"Lunn RM","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2005.11.018"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22580"},{"key":"e_1_2_7_41_1","first-page":"175","article-title":"A discussion of mechanisms of NO genotoxicity: implication of inhibition of DNA repair proteins","volume":"131","author":"Laval F","year":"1997","journal-title":"Rev Physiol Biochem Pharmacol"},{"key":"e_1_2_7_42_1","first-page":"3171","article-title":"Increased formation of oxidative DNA damage, 8\u2010hydroxydeoxyguanosine, in human livers with chronic hepatitis","volume":"54","author":"Shimoda R","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5414.651"},{"key":"e_1_2_7_44_1","first-page":"6012","article-title":"Abrogation of p53\u2010induced apoptosis by the hepatitis B virus X gene","volume":"55","author":"Wang XW","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14707"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20495"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037707"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947601911408889"},{"key":"e_1_2_7_49_1","first-page":"664","article-title":"Analysis of p53, K\u2010ras gene mutation & Helicobacter pylori infection in patients with gastric cancer & peptic ulcer disease at a tertiary care hospital in north India","volume":"136","author":"Saxena A","year":"2012","journal-title":"Indian J Med Res"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgq118"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(97)00352-2"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12460","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12460","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.12460","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T17:39:26Z","timestamp":1696268366000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.12460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,27]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1111\/liv.12460"],"URL":"https:\/\/doi.org\/10.1111\/liv.12460","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,27]]}}}