TY - JOUR
T1 - Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection
AU - Chan, K.Y.-K.
AU - Wong, C.-M.
AU - Kwan, J.S.-H.
AU - Lee, J.M.-F.
AU - Cheung, K.W.
AU - Yuen, M.F.
AU - Lai, C.L.
AU - Poon, R.T.-P.
AU - Sham, P.C.
AU - Ng, I.O.-L.
PY - 2011
Y1 - 2011
N2 - 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
AB - 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
U2 - 10.1371/journal.pone.0028798
DO - 10.1371/journal.pone.0028798
M3 - Article
C2 - 22174901
VL - 6
JO - PLoS ONE
JF - PLoS ONE
IS - 12
ER -
