title: Interleukin-1beta gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection.
abstract: Hepatitis C virus (HCV) infection is a major risk factor for developing hepatocellular carcinoma (HCC), a life-threatening sequel. However, the factors that affect disease progression to HCC have not been thoroughly elucidated. Genetic polymorphisms in proinflammatory cytokines, the interleukin 1 (IL-1) family (IL-1beta and IL-1ra) and tumor necrosis factor-alpha (TNF-alpha), were studied in 274 Japanese patients with chronic HCV infection and 55 healthy individuals using standard polymerase chain reaction-based genotyping techniques. The association between these polymorphisms and disease status was evaluated while controlling for confounding clinical variables. The proportion of patients with HCC in the IL-1beta-31 T/T (55%, odds ratio to C/C was 2.63, P =.009) genotype was higher than in the T/C (44%, odds ratio to C/C was 1.64, P =.149) and C/C genotypes (35%). The IL-1beta-31 and -511 loci were in near complete linkage disequilibrium, and the IL-1beta-511/-31 haplotype C-T was significantly associated with the presence of HCC (odds ratio of 1.51, P =.02). Polymorphisms in the TNF-alpha gene were not associated with disease. A multivariate analysis revealed that the IL-1beta-31 T/T genotype, alpha-fetoprotein >20 microg/L, presence of cirrhosis, male sex, and age >60 years were associated with the presence of HCC at odds ratios of 3.73 (T/T vs. C/C), 4.12, 4.03, 3.89, and 3.27, respectively. In conclusion, the IL-1beta-31 genotype T/T or the IL-1beta-511/-31 haplotype C-T is associated with the presence of HCC in Japanese patients with chronic HCV infection.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Japan.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Naoya
authors.initials: N
authors.lastname: Kato
authors.forename: Yujin
authors.initials: Y
authors.lastname: Hoshida
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Goto
authors.forename: Masaru
authors.initials: M
authors.lastname: Moriyama
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Otsuka
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Shiina
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shiratori
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ito
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha