title: Polymorphisms near the IFNL3 Gene Associated with HCV RNA Spontaneous Clearance and Hepatocellular Carcinoma Risk.
abstract: The aims of this study were to investigate associations between single nucleotide polymorphisms (SNPs) near the genes IFNL2, IFNL3, and IFNL4 and spontaneous clearance of hepatitis C virus (HCV) and to evaluate variants for their risk of hepatocellular carcinoma (HCC) among subjects in whom spontaneous HCV RNA clearance did not occur. In the first study, 889 untreated anti-HCV-seropositive patients without HCC symptoms were followed from 1991 to 2005. The spontaneous HCV clearance rate was found to be 33.1%. The TT variant of rs8099917 near IFNL3 was associated with increased spontaneous HCV RNA clearance, with an adjusted odds ratio (95% CI) of 2.78 (1.43-5.39), as was the newly-identified TT/TT dinucleotide variant rs368234815 near IFNL4 (adjusted odds ratio 2.68, 95% CI: 1.42-5.05). In the second study, associations between SNPs and HCC risk were examined in 483 HCC cases with detectable HCV RNA and 516 controls. In participants with HCV genotype 1, unfavorable genotypes for HCV clearance near IFNL3 were associated with increased HCC risk, the adjusted odds ratio (95% CI) for rs12979860 and rs8099917 being 1.73 (1.00-2.99) and 1.84 (1.02-3.33), respectively. Host characteristics should be considered to identify high-risk patients to prioritize the use of new antiviral agents and intensive screening.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Hwai-I
authors.initials: HI
authors.lastname: Yang
authors.affiliation: Division of Hepato-Gastroenterology, (Department of Internal Medicine), Kaohsiung Chang Gung Memorial Hospital, KaohsiungChang Gung University School of Medicine, Kaohsiung, Taiwan.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.|Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chin-Lan
authors.initials: CL
authors.lastname: Jen
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kang-Hsuan
authors.initials: KH
authors.lastname: Wong
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Soa-Yu
authors.initials: SY
authors.lastname: Chan
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Liang-Chun
authors.initials: LC
authors.lastname: Chen
authors.affiliation: MacKay Medical College, Taipei, Taiwan.
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, United States.|Yale University School of Medicine, New Haven, CT, United States.
authors.forename: Gilbert
authors.initials: G
authors.lastname: L'Italien
authors.affiliation: Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, United States.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.|Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei , Taiwan.
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000378:metabolism*; D012306:Risk; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human