Genetic Variation of <i>SAMM50</i> 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 <i>SAMM50</i> was linked to HCC. We aimed to validate this finding in a la...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/15353 |
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| author | Hans Dieter Nischalke Franziska Schmalz Stephan Buch Janett Fischer Christine Möller Madlen Matz-Soja Benjamin Krämer Bettina Langhans Alexandra Klüners Michael Soyka Felix Stickel Jacob Nattermann Thomas Berg Christian P. Strassburg Philipp Lutz |
| author_facet | Hans Dieter Nischalke Franziska Schmalz Stephan Buch Janett Fischer Christine Möller Madlen Matz-Soja Benjamin Krämer Bettina Langhans Alexandra Klüners Michael Soyka Felix Stickel Jacob Nattermann Thomas Berg Christian P. Strassburg Philipp Lutz |
| author_sort | Hans Dieter Nischalke |
| collection | DOAJ |
| 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 <i>SAMM50</i> 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 (<i>n</i> = 674) and with (<i>n</i> = 386) HCC, as well as controls with HCC due to viral hepatitis (<i>n</i> = 134), controls with heavy alcohol abuse without liver disease (<i>n</i> = 266) and healthy subjects (<i>n</i> = 237), were genotyped for <i>SAMM50</i> rs3827385 and rs3761472 and for <i>PNPLA3</i> rs738409. Genotype frequencies were compared between patients with alcohol-associated cirrhosis with and without HCC by uni- and multivariate analysis. Minor variants in both <i>SAMM50</i> 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 <i>PNPLA3</i> rs738409. The univariate analysis resulted in an odds ratio (OR) of 1.8 for carriers of at least one minor variant of <i>SAMM50</i> rs3827385 and rs3761472 (each <i>p</i> < 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 <i>PNPLA3</i> 148M (OR 2.1) remaining in the final model. Although minor variants of both <i>SAMM50</i> loci are strongly associated with alcoholic HCC, this association is not independent of carriage of the well-known risk variant <i>PNPLA3</i> 148M. |
| first_indexed | 2024-03-09T17:44:33Z |
| format | Article |
| id | doaj.art-78bae394fe044d57bbc1382b8559abd0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:44:33Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-78bae394fe044d57bbc1382b8559abd02023-11-24T11:17:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231535310.3390/ijms232315353Genetic Variation of <i>SAMM50</i> Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian PatientsHans Dieter Nischalke0Franziska Schmalz1Stephan Buch2Janett Fischer3Christine Möller4Madlen Matz-Soja5Benjamin Krämer6Bettina Langhans7Alexandra Klüners8Michael Soyka9Felix Stickel10Jacob Nattermann11Thomas Berg12Christian P. Strassburg13Philipp Lutz14Department of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, GermanyDepartment of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, GermanyDepartment of Medicine I, Dresden University Hospital, 01307 Dresden, GermanyDivision of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103 Leipzig, GermanyDepartment of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, GermanyDivision of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103 Leipzig, GermanyDepartment of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, GermanyDepartment of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, GermanyDepartment of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, GermanyPsychiatric Hospital, Ludwig Maximilians University, 80336 Munich, GermanyDepartment of Gastroenterology and Hepatology, University Hospital of Zürich, 8091 Zürich, SwitzerlandDepartment of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, GermanyDivision of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103 Leipzig, GermanyDepartment of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, GermanyDepartment of Internal Medicine I, University Hospital, University of Bonn, 53127 Bonn, GermanyHepatocellular 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 <i>SAMM50</i> 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 (<i>n</i> = 674) and with (<i>n</i> = 386) HCC, as well as controls with HCC due to viral hepatitis (<i>n</i> = 134), controls with heavy alcohol abuse without liver disease (<i>n</i> = 266) and healthy subjects (<i>n</i> = 237), were genotyped for <i>SAMM50</i> rs3827385 and rs3761472 and for <i>PNPLA3</i> rs738409. Genotype frequencies were compared between patients with alcohol-associated cirrhosis with and without HCC by uni- and multivariate analysis. Minor variants in both <i>SAMM50</i> 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 <i>PNPLA3</i> rs738409. The univariate analysis resulted in an odds ratio (OR) of 1.8 for carriers of at least one minor variant of <i>SAMM50</i> rs3827385 and rs3761472 (each <i>p</i> < 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 <i>PNPLA3</i> 148M (OR 2.1) remaining in the final model. Although minor variants of both <i>SAMM50</i> loci are strongly associated with alcoholic HCC, this association is not independent of carriage of the well-known risk variant <i>PNPLA3</i> 148M.https://www.mdpi.com/1422-0067/23/23/15353cirrhosisalcohol-associated liver diseaseHCC<i>SAMM50</i> |
| spellingShingle | Hans Dieter Nischalke Franziska Schmalz Stephan Buch Janett Fischer Christine Möller Madlen Matz-Soja Benjamin Krämer Bettina Langhans Alexandra Klüners Michael Soyka Felix Stickel Jacob Nattermann Thomas Berg Christian P. Strassburg Philipp Lutz Genetic Variation of <i>SAMM50</i> Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients International Journal of Molecular Sciences cirrhosis alcohol-associated liver disease HCC <i>SAMM50</i> |
| title | Genetic Variation of <i>SAMM50</i> Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients |
| title_full | Genetic Variation of <i>SAMM50</i> Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients |
| title_fullStr | Genetic Variation of <i>SAMM50</i> Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients |
| title_full_unstemmed | Genetic Variation of <i>SAMM50</i> Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients |
| title_short | Genetic Variation of <i>SAMM50</i> Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients |
| title_sort | genetic variation of i samm50 i is not an independent risk factor for alcoholic hepatocellular carcinoma in caucasian patients |
| topic | cirrhosis alcohol-associated liver disease HCC <i>SAMM50</i> |
| url | https://www.mdpi.com/1422-0067/23/23/15353 |
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