title: Association of interleukin-28B genotype and hepatocellular carcinoma recurrence in patients with chronic hepatitis C.
abstract: OBJECTIVE
  Several single-nucleotide polymorphisms (SNP) in the interleukin-28B (IL-28B) locus have recently been shown to be associated with antiviral treatment efficacy for chronic hepatitis C (CHC). However, such an association with hepatocellular carcinoma (HCC) is unkno3 we investigated the association between the IL-28B genotype and the biology and clinical outcome of patients with HCC receiving curative treatment.
  
  
  METHODS
  Genotyping of 183 patients with HCC with CHC who were treated with hepatic resection or radiofrequency ablation (RFA) was carried out, and the results were analyzed to determine the association between the IL-28B genotype (rs8099917) and clinical outcome. Gene expression profiles of 20 patients with HCC and another series of 91 patients with CHC were analyzed using microarray analysis and gene set enrichment analysis. Histologic and immunohistochemical analyses were also conducted.
  
  
  RESULTS
  The TT, TG, and GG proportions of the rs8099917 genotype were 67.8% (124 of 183), 30.6% (56 of 183), and 1.6% (3 of 183), respectively. Multivariate Cox proportional hazard analysis showed that the IL-28B TT genotype was significantly associated with HCC recurrence (P = 0.007; HR, 2.674; 95% confidence interval, 1.16-2.63). Microarray analysis showed high expression levels of IFN-stimulated genes in background liver samples and immune-related genes in tumor tissues of the IL-28B TG/GG genotype. Histologic findings showed that more lymphocytes infiltrated into tumor tissues in the TG/GG genotype.
  
  
  CONCLUSIONS
  The IL-28B genotype is associated with HCC recurrence, gene expression, and histologic findings in patients with CHC.
authors: Department of Gastroenterology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors: Yuji
authors: Y
authors: Hodo
authors: Masao
authors: M
authors: Honda
authors: Akihiro
authors: A
authors: Tanaka
authors: Yoshimoto
authors: Y
authors: Nomura
authors: Kuniaki
authors: K
authors: Arai
authors: Taro
authors: T
authors: Yamashita
authors: Yoshio
authors: Y
authors: Sakai
authors: Tatsuya
authors: T
authors: Yamashita
authors: Eishiro
authors: E
authors: Mizukoshi
authors: Akito
authors: A
authors: Sakai
authors: Motoko
authors: M
authors: Sasaki
authors: Yasuni
authors: Y
authors: Nakanuma
authors: Mitsuhiko
authors: M
authors: Moriyama
authors: Shuichi
authors: S
authors: Kaneko
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000150:complications* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda