PLoS ONE (Jan 2012)

A 3' UTR SNP in COL18A1 is associated with susceptibility to HBV related hepatocellular carcinoma in Chinese: three independent case-control studies.

  • Xiaopan Wu,
  • Jia Wu,
  • Zhenhui Xin,
  • Huifen Wang,
  • Xilin Zhu,
  • Liping Pan,
  • Zhuo Li,
  • Hui Li,
  • Ying Liu

DOI
https://doi.org/10.1371/journal.pone.0033855
Journal volume & issue
Vol. 7, no. 3
p. e33855

Abstract

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BACKGROUND: Accumulated evidences indicate that single nucleotide polymorphisms (SNP) in angiogenesis and tumorigenesis related genes are associated with risk of Hepatocellular carcinoma (HCC). COL18A1 encodes the precursor of endostatin, which is a broad-spectrum angiogenesis inhibitor, and we speculate that SNPs in COL18A1 may be associated with susceptibility to HCC. METHODS AND FINDINGS: We carried out a 2-stage association study in 3 independent case-control groups in a total of 1067 chronic hepatitis B (CHB) patients and 808 hepatitis B virus (HBV) related HCC patients in Han Chinese. Four SNPs which can represent all potential functional SNPs with MAF>0.1 recorded in HapMap database were genotyped using TaqMan methods. Levels of total COL18A1 mRNA were also examined using quantitative real-time RT-PCR. We found that rs7499 located in 3'-UTR to be strongly associated with HBV related HCC (P(combined) = 0.0000005, OR = 0.72, 95%CI = 0.63-0.82). COL18A1 mRNA expression was significantly decreased as the disease progressed (P = 0.000026). CONCLUSION: These findings indicate that COL18A1 rs7499 may contribute to the risk of HCC in Han Chinese.