Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection

PLoS One. 2011;6(12):e28798. doi: 10.1371/journal.pone.0028798. Epub 2011 Dec 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian Continental Ancestry Group / genetics*
  • Base Sequence
  • Carcinoma, Hepatocellular / complications*
  • Carcinoma, Hepatocellular / genetics*
  • Cell Line, Tumor
  • China
  • Chromosomes, Human, Pair 8 / genetics
  • Computational Biology
  • Data Mining
  • Expressed Sequence Tags
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Loci / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / genetics*
  • Humans
  • Liver Neoplasms / complications
  • Liver Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Reproducibility of Results