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Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients

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 patie...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740343/
https://www.ncbi.nlm.nih.gov/pubmed/36499681
http://dx.doi.org/10.3390/ijms232315353
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author 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
author_facet 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
author_sort Nischalke, Hans Dieter
collection PubMed
description 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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spelling pubmed-97403432022-12-11 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 Int J Mol Sci Article 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. MDPI 2022-12-05 /pmc/articles/PMC9740343/ /pubmed/36499681 http://dx.doi.org/10.3390/ijms232315353 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients
title Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients
title_full Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients
title_fullStr Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients
title_full_unstemmed Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients
title_short Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients
title_sort genetic variation of samm50 is not an independent risk factor for alcoholic hepatocellular carcinoma in caucasian patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740343/
https://www.ncbi.nlm.nih.gov/pubmed/36499681
http://dx.doi.org/10.3390/ijms232315353
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