Open Access

Nine susceptibility loci for hepatitis B virus-related hepatocellular carcinoma identified by a pilot two-stage genome-wide association study

  • Authors:
    • Li‑Shuai Qu
    • Fei Jin
    • Yan‑Mei Guo
    • Tao‑Tao Liu
    • Ru‑Yi Xue
    • Xiao‑Wu Huang
    • Min Xu
    • Tao‑Yang Chen
    • Zheng‑Ping Ni
    • Xi‑Zhong Shen
  • View Affiliations

  • Published online on: November 23, 2015     https://doi.org/10.3892/ol.2015.3958
  • Pages: 624-632
  • Copyright: © Qu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have indicated that complex interactions among viral, environmental and genetic factors lead to hepatocellular carcinoma (HCC). To identify susceptibility alleles for hepatitis B virus (HBV)‑related HCC, the present study conducted a pilot two‑phase genome‑wide association study (GWAS) in 660 Han Chinese individuals. In phase 1, a total of 500,447 single‑nucleotide polymorphisms (SNPs) were genotyped in 50 HCC cases and 50 controls using Affymetrix GeneChip 500k Array Set. In phase 2, 1,152 SNPs were selected from phase 1 and genotyped in 282 cases and 278 controls using the Illumina GoldenGate platform. The prior probability of HCC in control subjects was assigned at 0.01, and false‑positive report probability (FPRP) was utilized to evaluate the statistical significance. In phase 1, one SNP (rs2212522) showed a significant association with HCC (Pallele=5.23x10‑8; ORallele=4.96; 95% CI, 2.72‑9.03). In phase 2, among 27 SNPs with unadjusted Pallele<0.05, 9 SNPs were associated with HCC based on FPRP criteria (FPRP <0.20). The strongest statistical evidence for an association signal was with rs2120243 (combined ORallele=1.76; 95% CI, 1.39‑2.22; P=2.00x10‑6), which maps within the fourth intron of VEPH1. The second strongest statistical evidence for an association was identified for rs1350171 (combined ORallele=1.66; 95% CI, 1.33‑2.07; P=6.48x10‑6), which maps to the region downstream of the FZD4 gene. The other potential susceptibility genes included PCDH9, PRMT6, LHX1, KIF2B and L3MBTL4. In conclusion, this pilot two‑phase GWAS provides the evidence for the existence of common susceptibility loci for HCC. These genes involved various signaling pathways, including those associated with transforming growth factor β, insulin/phosphoinositide 3 kinase, Wnt and epidermal growth factor receptor. These associations must be replicated and validated in larger studies.
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January-2016
Volume 11 Issue 1

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Copy and paste a formatted citation
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Spandidos Publications style
Qu LS, Jin F, Guo YM, Liu TT, Xue RY, Huang XW, Xu M, Chen TY, Ni ZP, Shen XZ, Shen XZ, et al: Nine susceptibility loci for hepatitis B virus-related hepatocellular carcinoma identified by a pilot two-stage genome-wide association study. Oncol Lett 11: 624-632, 2016
APA
Qu, L., Jin, F., Guo, Y., Liu, T., Xue, R., Huang, X. ... Shen, X. (2016). Nine susceptibility loci for hepatitis B virus-related hepatocellular carcinoma identified by a pilot two-stage genome-wide association study. Oncology Letters, 11, 624-632. https://doi.org/10.3892/ol.2015.3958
MLA
Qu, L., Jin, F., Guo, Y., Liu, T., Xue, R., Huang, X., Xu, M., Chen, T., Ni, Z., Shen, X."Nine susceptibility loci for hepatitis B virus-related hepatocellular carcinoma identified by a pilot two-stage genome-wide association study". Oncology Letters 11.1 (2016): 624-632.
Chicago
Qu, L., Jin, F., Guo, Y., Liu, T., Xue, R., Huang, X., Xu, M., Chen, T., Ni, Z., Shen, X."Nine susceptibility loci for hepatitis B virus-related hepatocellular carcinoma identified by a pilot two-stage genome-wide association study". Oncology Letters 11, no. 1 (2016): 624-632. https://doi.org/10.3892/ol.2015.3958