TRAIL receptor I (DR4) polymorphisms C626G and A683C are associated with an increased risk for hepatocellular carcinoma (HCC) in HCV-infected patients

BMC Cancer

Research Article

Thomas Berg¹  Christian Körner²  Andreas Glässner²  Marianne Eisenhardt²  Katarina Riesner²  Benjamin Krämer²  Tilman Sauerbruch²  Franziska Wolter²  Jacob Nattermann²  Hans Dieter Nischalke²  Ulrich Spengler²  Tobias Müller³ 

[1]Department of Gastroenterology, University Hospital Leipzig, Philipp-Rosenthal-Strasse 27, 04103, Leipzig, Germany

[2]Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

[3]Medical Clinic for Hepatology and Gastroenterology, Medical University Charité, Augustenburger Platz 1, 13353, Berlin, Germany

关键词: TRAIL receptor I;    DR4;    Apoptosis;    Polymorphism;    C626G (rs20575);    A683C (rs20576);    HCV;    HCC;    Cancer;   

DOI  :  10.1186/1471-2407-12-85

 received in 2011-08-30, accepted in 2012-03-08,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundTumour surveillance via induction of TRAIL-mediated apoptosis is a key mechanism, how the immune system prevents malignancy. To determine if gene variants in the TRAIL receptor I (DR4) gene affect the risk of hepatitis C virus (HCV)-induced liver cancer (HCC), we analysed DR4 mutations C626G (rs20575) and A683C (rs20576) in HCV-infected patients with and without HCC.MethodsFrequencies of DR4 gene polymorphisms were determined by LightSNiP assays in 159 and 234 HCV-infected patients with HCC and without HCC, respectively. 359 healthy controls served as reference population.ResultsDistribution of C626G and A683C genotypes were not significantly different between healthy controls and HCV-positive patients without HCC. DR4 variants 626C and 683A occurred at increased frequencies in patients with HCC. The risk of HCC was linked to carriage of the 626C allele and the homozygous 683AA genotype, and the simultaneous presence of the two risk variants was confirmed as independent HCC risk factor by Cox regression analysis (Odds ratio 1.975, 95% CI 1.205-3.236; p = 0.007). Furthermore HCV viral loads were significantly increased in patients who simultaneously carried both genetic risk factors (2.69 ± 0.36 × 106 IU/ml vs. 1.81 ± 0.23 × 106 IU/ml, p = 0.049).ConclusionsThe increased prevalence of patients with a 626C allele and the homozygous 683AA genotype in HCV-infected patients with HCC suggests that these genetic variants are a risk factor for HCC in chronic hepatitis C.

【 授权许可】

Unknown   
© Körner et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.