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Open Access Research article

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

Christian Körner1, Katarina Riesner1, Benjamin Krämer1, Marianne Eisenhardt1, Andreas Glässner1, Franziska Wolter1, Thomas Berg2, Tobias Müller3, Tilman Sauerbruch1, Jacob Nattermann1, Ulrich Spengler1 and Hans Dieter Nischalke1*

Author Affiliations

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

2 Department of Gastroenterology, University Hospital Leipzig, Philipp-Rosenthal-Strasse 27, 04103 Leipzig, Germany

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

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BMC Cancer 2012, 12:85  doi:10.1186/1471-2407-12-85

Published: 8 March 2012

Abstract

Background

Tumour 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.

Methods

Frequencies 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.

Results

Distribution 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).

Conclusions

The 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.

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