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Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients.
Nischalke, Hans Dieter; Schmalz, Franziska; Buch, Stephan; Fischer, Janett; Möller, Christine; Matz-Soja, Madlen; Krämer, Benjamin; Langhans, Bettina; Klüners, Alexandra; Soyka, Michael; Stickel, Felix; Nattermann, Jacob; Berg, Thomas; Strassburg, Christian P; Lutz, Philipp.
Afiliación
  • Nischalke HD; Department of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, Germany.
  • Schmalz F; Department of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, Germany.
  • Buch S; Department of Medicine I, Dresden University Hospital, 01307 Dresden, Germany.
  • Fischer J; Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103 Leipzig, Germany.
  • Möller C; Department of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, Germany.
  • Matz-Soja M; Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103 Leipzig, Germany.
  • Krämer B; Department of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, Germany.
  • Langhans B; Department of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, Germany.
  • Klüners A; Department of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, Germany.
  • Soyka M; Psychiatric Hospital, Ludwig Maximilians University, 80336 Munich, Germany.
  • Stickel F; Department of Gastroenterology and Hepatology, University Hospital of Zürich, 8091 Zürich, Switzerland.
  • Nattermann J; Department of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, Germany.
  • Berg T; Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103 Leipzig, Germany.
  • Strassburg CP; Department of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, Germany.
  • Lutz P; Department of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, Germany.
Int J Mol Sci ; 23(23)2022 Dec 05.
Article en En | MEDLINE | ID: mdl-36499681
Hepatocellular carcinoma (HCC) is a severe complication of advanced alcoholic liver disease, which is modulated by genetic predisposition. Identifying new genetic loci might improve screening. Genetic variation of SAMM50 was linked to HCC. We aimed to validate this finding in a large cohort of patients with advanced alcoholic liver disease (ALD). A large, well-characterised cohort of patients with alcoholic cirrhosis without (n = 674) and with (n = 386) HCC, as well as controls with HCC due to viral hepatitis (n = 134), controls with heavy alcohol abuse without liver disease (n = 266) and healthy subjects (n = 237), were genotyped for SAMM50 rs3827385 and rs3761472 and for PNPLA3 rs738409. Genotype frequencies were compared between patients with alcohol-associated cirrhosis with and without HCC by uni- and multivariate analysis. Minor variants in both SAMM50 rs3827385 and rs3761472 were significantly more frequent in patients with alcoholic HCC versus alcoholic cirrhosis and versus the control cohorts. An even stronger association was noted for PNPLA3 rs738409. The univariate analysis resulted in an odds ratio (OR) of 1.8 for carriers of at least one minor variant of SAMM50 rs3827385 and rs3761472 (each p < 0.001), but this association was lost in multivariate analysis with age (OR 1.1/year), male sex (OR 3.2), diabetes (OR 1.9) and carriage of PNPLA3 148M (OR 2.1) remaining in the final model. Although minor variants of both SAMM50 loci are strongly associated with alcoholic HCC, this association is not independent of carriage of the well-known risk variant PNPLA3 148M.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza