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

PLoS One. 2012;7(3):e33855. doi: 10.1371/journal.pone.0033855. Epub 2012 Mar 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Adult
  • Asian People / genetics
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / ethnology
  • Carcinoma, Hepatocellular / genetics*
  • Case-Control Studies
  • China
  • Collagen Type XVIII / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • HapMap Project
  • Haplotypes
  • Hepatitis B / complications
  • Humans
  • Linkage Disequilibrium
  • Liver Neoplasms / complications
  • Liver Neoplasms / ethnology
  • Liver Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors


  • 3' Untranslated Regions
  • Collagen Type XVIII