Association of Interleukin 28B genotype and hepatocellular carcinoma recurrence in patients with chronic hepatitis C Authors:

Purpose: Several single nucleotide polymorphisms (SNPs) in the interleukin 28B (IL28B) locus have recently been shown to be associated with antiviral treatment efficacy for chronic hepatitis C (CH-C). However, such an association with hepatocellular carcinoma (HCC) is unknown. Here, we investigated the association between the IL28B genotype and the biology and clinical outcome of HCC patients receiving curative treatment. Experimental Design: Genotyping of 183 HCC patients with CH-C who were treated with hepatic resection or radiofrequency ablation (RFA) was carried out, and the results were analyzed to determine the association between the IL28B genotype (rs8099917) and clinical outcome. Gene expression profiles of 20 HCC patients and another series of 91 CH-C patients were analyzed using microarray analysis and gene set enrichment analysis. Histological and immunohistochemical analyses were also performed. Results: The TT, TG and GG proportions of the rs8099917 genotype were 67.8% (124/183), 30.6% (56/183) and 1.6% (3/183), respectively. Multivariate Cox proportional hazard analysis demonstrated that the IL28B TT genotype was significantly associated with HCC recurrence (p = 0.007; hazard ratio, 2.674; 95% CI, 1.16-2.63). Microarray analysis showed high expression levels of interferon-stimulated genes in background liver samples and immune-related genes in tumor tissues of the IL28B TG/GG genotype. Histological findings showed that more lymphocytes infiltrated into tumor tissues in the TG/GG genotype. Conclusions: The IL28B genotype is associated with HCC recurrence, gene expression and histological findings in patients with CH-C. Research. on November 12, 2017. © 2013 American Association for Cancer clincancerres.aacrjournals.org Downloaded from Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on February 20, 2013; DOI: 10.1158/1078-0432.CCR-12-1641