PLoS ONE (Jan 2011)

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

  • Kelvin Yuen-Kwong Chan,
  • Chun-Ming Wong,
  • Johnny Sheung-Him Kwan,
  • Joyce Man-Fong Lee,
  • Ka Wai Cheung,
  • Man Fung Yuen,
  • Ching Lung Lai,
  • Ronnie Tung-Ping Poon,
  • Pak Chung Sham,
  • Irene Oi-Lin Ng

DOI
https://doi.org/10.1371/journal.pone.0028798
Journal volume & issue
Vol. 6, no. 12
p. e28798

Abstract

Read online

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.