title: Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection.
abstract: One of the most relevant risk factors for hepatocellular carcinoma (HCC) development is chronic hepatitis B virus (HBV) infection, but only a fraction of chronic HBV carriers develop HCC, indicating that complex interactions among viral, environmental and genetic factors lead to HCC in HBV-infected patients. So far, host genetic factors have incompletely been characterized. Therefore, we performed a genome-wide association (GWA) study in a Southern Chinese cohort consisting of 95 HBV-infected HCC patients (cases) and 97 HBV-infected patients without HCC (controls) using the Illumina Human610-Quad BeadChips. The top single nucleotide polymorphisms (SNPs) were then validated in an independent cohort of 500 cases and 728 controls. 4 SNPs (rs12682266, rs7821974, rs2275959, rs1573266) at chromosome 8p12 showed consistent association in both the GWA and replication phases (OR(combined) = 1.31-1.39; p(combined) = 2.71 × 10(-5)-5.19 × 10(-4); PAR(combined) = 26-31%). We found a 2.3-kb expressed sequence tag (EST) in the region using in-silico data mining and verified the existence of the full-length EST experimentally. The expression level of the EST was significantly reduced in human HCC tumors in comparison to the corresponding non-tumorous liver tissues (P<0.001). Results from sequence analysis and in-vitro protein translation study suggest that the transcript might function as a long non-coding RNA. In summary, our study suggests that variations at chromosome 8p12 may promote HCC in patients with HBV. Further functional studies of this region may help understand HBV-associated hepatocarcinogenesis.
authors.affiliation: State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong.
authors.forename: Kelvin Yuen-Kwong
authors.initials: KY
authors.lastname: Chan
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Wong
authors.forename: Johnny Sheung-Him
authors.initials: JS
authors.lastname: Kwan
authors.forename: Joyce Man-Fong
authors.initials: JM
authors.lastname: Lee
authors.forename: Ka Wai
authors.initials: KW
authors.lastname: Cheung
authors.forename: Man Fung
authors.initials: MF
authors.lastname: Yuen
authors.forename: Ching Lung
authors.initials: CL
authors.lastname: Lai
authors.forename: Ronnie Tung-Ping
authors.initials: RT
authors.lastname: Poon
authors.forename: Pak Chung
authors.initials: PC
authors.lastname: Sham
authors.forename: Irene Oi-Lin
authors.initials: IO
authors.lastname: Ng
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000235:genetics*; D045744:Cell Line, Tumor; D002681:China; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D019295:Computational Biology; D057225:Data Mining; D020224:Expressed Sequence Tags; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results