title: TRAIL receptor I (DR4) polymorphisms C626G and A683C are associated with an increased risk for hepatocellular carcinoma (HCC) in HCV-infected patients.
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 × 10(6) IU/ml vs. 1.81 ± 0.23 × 10(6) 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.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str, 25, 53127 Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Körner
authors.forename: Katarina
authors.initials: K
authors.lastname: Riesner
authors.forename: Benjamin
authors.initials: B
authors.lastname: Krämer
authors.forename: Marianne
authors.initials: M
authors.lastname: Eisenhardt
authors.forename: Andreas
authors.initials: A
authors.lastname: Glässner
authors.forename: Franziska
authors.initials: F
authors.lastname: Wolter
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Tobias
authors.initials: T
authors.lastname: Müller
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Jacob
authors.initials: J
authors.lastname: Nattermann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.forename: Hans Dieter
authors.initials: HD
authors.lastname: Nischalke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand