title: A variant in myeloperoxidase promoter hastens the emergence of hepatocellular carcinoma in patients with HCV-related cirrhosis.
abstract: OBJECTIVE
  Genetic dimorphisms modulate the activities of several pro- or antioxidant enzymes, including myeloperoxidase (MPO), catalase (CAT), manganese superoxide dismutase (SOD2), and glutathione peroxidase 1 (GPx1). We assessed the role of the G(-463)A-MPO, T(-262)C-CAT, Ala16Val-SOD2, and Pro198Leu-GPx1 variants in modulating HCC development in patients with HCV-induced cirrhosis.
  
  
  METHODS
  Two hundred and five patients with HCV-induced, biopsy-proven cirrhosis but without detectable HCC at inclusion were prospectively followed-up for HCC development. The influence of various genotypes on HCC occurrence was assessed with the Kaplan-Meier method.
  
  
  RESULTS
  During follow-up (103.2±3.4 months), 84 patients (41%) developed HCC, and 66 died. Whereas the Ala16Val-SOD2 or Pro198Leu-GPx1 dimorphisms did not modulate the risk, HCC occurrence was increased in patients with either the homozygous GG-MPO genotype (HR=2.8 [1.7-4.4]; first quartile time to HCC occurrence: 45 vs. 96 months; LogRank <0.0001) or the homozygous CC-CAT genotype (HR=1.74 [1.06-2.82]; first quartile time to HCC occurrence: 55 vs. 96 months; LogRank=0.02). Compared to patients with neither of these two at risk factors, patients with only the CC-CAT genotype had a HR of 2.05 [0.9-4.6] (p=0.08) and patients with only the GG-MPO genotype had a HR of 3.8 [1.5-9.1] (p=0.002), while patients with both risk factors had an HR of 4.8 [2.2-10.4] (p<0.0001). However, only the GG-MPO genotype was independently associated with the HCC risk in multivariate Cox analysis.
  
  
  CONCLUSIONS
  The high activity-associated GG-MPO genotype increases the rate of HCC occurrence in patients with HCV-induced cirrhosis.
authors: Service d'Hépatologie, Hôpital Jean Verdier, AP-HP, Bondy, France. pierre.nahon@jvr.aphp.fr
authors: Pierre
authors: P
authors: Nahon
authors: Angela
authors: A
authors: Sutton
authors: Pierre
authors: P
authors: Rufat
authors: Nathalie
authors: N
authors: Charnaux
authors: Abdellah
authors: A
authors: Mansouri
authors: Richard
authors: R
authors: Moreau
authors: Nathalie
authors: N
authors: Ganne-Carrié
authors: Véronique
authors: V
authors: Grando-Lemaire
authors: Gisèle
authors: G
authors: N'Kontchou
authors: Jean-Claude
authors: JC
authors: Trinchet
authors: Dominique
authors: D
authors: Pessayre
authors: Michel
authors: M
authors: Beaugrand
mesh_terms: D019943:Amino Acid Substitution; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D002374:Catalase / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000209:etiology; D008113:Liver Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2
chemical_list: D002374:Catalase; D005979:Glutathione Peroxidase; D009195:Peroxidase; D013482:Superoxide Dismutase; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2; C000722067:GPX1 protein, human