title: Chemokine RANTES promoter dimorphisms and hepatocellular carcinoma occurrence in patients with alcoholic or hepatitis C virus-related cirrhosis.
abstract: BACKGROUND
  This study explores the influence of two functional genetic polymorphisms in the regulated on activation in normal T-cell expressed and secreted(RANTES) promoter on the risk of hepatocellular carcinoma (HCC) occurrence in patients with alcoholic or Hepatitis C Virus (HCV)-related cirrhosis.
  
  
  METHODS
  RANTES C-28G and G-403A promoter dimorphisms and RANTES serum levels were assessed in 243 HCV-infected patients and 253 alcoholic patients, included at the time of diagnosis of cirrhosis and prospectively followed-up.
  
  
  RESULTS
  During a mean follow-up time of 76 months, 137 (27.6%) patients developed HCC and 170 (34.2%) died or were transplanted. During follow-up, patients with alcoholic cirrhosis and bearing two copies of the RANTES G-403 variant (2G-403 genotype, n = 156/253) had a higher rate of HCC occurrence compared with patients carrying at least one RANTES A-403 allele (26.3% vs. 8.2%, P = 0.0004). The RANTES 2G-403 genotype was a risk factor for HCC occurrence [HR = 3.0 (1.3-5.8); first quartile time to HCC occurrence: 60 vs. 120 months; LogRank = 0.007] and death [HR = 1.4 (1.0-2.0); median time to death: 55 vs. 79 months; LogRank = 0.01] in this subgroup. Carriage of the RANTES 2G-403 genotype was not associated with HCC development or death in patients with HCV-related cirrhosis. The RANTES C-28G dimorphism did not influence the occurrence of death or HCC in either cohort of patients.
  
  
  CONCLUSIONS
  This study suggests an influence of the chemokine RANTES G-403A dimorphism on the occurrence of HCC in patients with alcoholic cirrhosis.
  
  
  CONCLUSIONS
  Our findings provide clues for future studies on RANTES gene in relation to HCC susceptibility.
authors: University Paris 13-UFR SMBH/INSERM U698, Bobigny, France.
authors: Faten
authors: F
authors: Charni
authors: Angela
authors: A
authors: Sutton
authors: Pierre
authors: P
authors: Rufat
authors: Christelle
authors: C
authors: Laguillier
authors: Abdellah
authors: A
authors: Mansouri
authors: Richard
authors: R
authors: Moreau
authors: Nathalie
authors: N
authors: Ganne-Carrié
authors: Jean-Claude
authors: JC
authors: Trinchet
authors: Michel
authors: M
authors: Beaugrand
authors: Nathalie
authors: N
authors: Charnaux
authors: Pierre
authors: P
authors: Nahon