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dc.contributor.authorTanabe, Kenneth Kenji
dc.contributor.authorLemoine, Antoinette
dc.contributor.authorFinkelstein, Dianne Madelyn
dc.contributor.authorKawasaki, Hiroshi
dc.contributor.authorFujii, Tsutomu
dc.contributor.authorChung, Raymond Taeyong
dc.contributor.authorLauwers, Gregory Y.
dc.contributor.authorKulu, Yakup
dc.contributor.authorMuzikansky, Alona
dc.contributor.authorKuruppu, Darshini
dc.contributor.authorLanuti, Michael
dc.contributor.authorGoodwin, Jonathan M.
dc.contributor.authorAzoulay, Daniel
dc.contributor.authorFuchs, Bryan C.
dc.date.accessioned2018-03-27T17:31:41Z
dc.date.issued2008
dc.identifier.citationTanabe, Kenneth K., Antoinette Lemoine, Dianne M. Finkelstein, Hiroshi Kawasaki, Tsutomu Fujii, Raymond T. Chung, Gregory Y. Lauwers, et al. 2008. “Epidermal Growth Factor Gene Functional Polymorphism and the Risk of Hepatocellular Carcinoma in Patients With Cirrhosis.” JAMA 299 (1) (January 2). doi:10.1001/jama.2007.65.en_US
dc.identifier.issn0098-7484en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:35140956
dc.description.abstractContext: Overexpression of epidermal growth factor (EGF) in the liver induces transformation to hepatocellular carcinoma in animal models. Polymorphisms in the EGF gene modulate EGF levels. Objective: To assess the relationship among human EGF gene single-nucleotide polymorphism, EGF expression, and risk of hepatocellular carcinoma. Design, Setting, and Participants: Molecular mechanisms linking the 61*G allele polymorphism to EGF expression were examined in human hepatocellular carcinoma cell lines and human liver tissue. A case-control study involving 207 patients with cirrhosis was conducted at the Massachusetts General Hospital (1999-2006) and a validation case-control study involving 121 patients with cirrhosis was conducted at Hôpital Paul Brousse (1993-2006). Restriction fragment-length polymorphism was used to determine the EGF gene polymorphism genotype. Logistic regression analysis was used to assess the association between the EGF polymorphism and hepatocellular carcinoma risk. Main Outcome Measures: Mechanisms by which the EGF gene polymorphism modulates EGF levels and associations among EGF gene polymorphism, EGF levels, and hepatocellular carcinoma. Results: Transcripts from the EGF 61*G allele exhibited more than a 2-fold longer half-life than those from the 61*A allele, and EGF secretion was 2.3-fold higher in G/G hepatocellular carcinoma cell lines than A/A cell lines. Serum EGF levels were 1.8-fold higher in G/G patients than A/A patients, and liver EGF levels were 2.4-fold higher in G/G patients than A/A patients. Among the 207 patients with cirrhosis in the Massachusetts study population, 59 also had hepatocellular carcinoma. Analysis of the distribution of allelic frequencies revealed that there was a 4-fold odds of hepatocellular carcinoma in G/G patients compared with A/A patients in the Massachusetts study population (odds ratio, 4.0; 95% confidence interval [CI], 1.6-9.6; P = .002). Logistic regression analysis demonstrated that the number of copies of G was significantly associated with hepatocellular carcinoma after adjusting for age, sex, race, etiology, and severity of cirrhosis (G/G or A/G vs A/A; hazard ratio, 3.49; 95% CI, 1.29-9.44; P = .01). The significant association was validated in the French patients with alcoholic cirrhosis and hepatocellular carcinoma. Conclusion: The EGF gene polymorphism genotype is associated with risk for development of hepatocellular carcinoma in liver cirrhosis through modulation of EGF levels.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Medical Association (AMA)en_US
dc.relation.isversionofdoi:10.1001/jama.2007.65en_US
dash.licenseMETA_ONLY
dc.titleEpidermal Growth Factor Gene Functional Polymorphism and the Risk of Hepatocellular Carcinoma in Patients With Cirrhosisen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalJAMAen_US
dash.depositing.authorLauwers, Gregory Y.
dash.embargo.until10000-01-01
dc.identifier.doi10.1001/jama.2007.65*
dash.authorsorderedfalse
dash.contributor.affiliatedTanabe, Kenneth
dash.contributor.affiliatedFuchs, Bryan
dash.contributor.affiliatedLauwers, Gregory Y.
dash.contributor.affiliatedChung, Raymond
dash.contributor.affiliatedKuruppu, Darshini
dash.contributor.affiliatedFinkelstein, Dianne
dash.contributor.affiliatedLanuti, Michael


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