title: A 3' UTR SNP in COL18A1 is associated with susceptibility to HBV related hepatocellular carcinoma in Chinese: three independent case-control studies.
abstract: 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  These findings indicate that COL18A1 rs7499 may contribute to the risk of HCC in Han Chinese.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Wu
authors.forename: Jia
authors.initials: J
authors.lastname: Wu
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Xin
authors.forename: Huifen
authors.initials: H
authors.lastname: Wang
authors.forename: Xilin
authors.initials: X
authors.lastname: Zhu
authors.forename: Liping
authors.initials: L
authors.lastname: Pan
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D043170:Collagen Type XVIII / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D060148:HapMap Project; D006239:Haplotypes; D006509:Hepatitis B / Q000150:complications; D006801:Humans; D015810:Linkage Disequilibrium; D008113:Liver Neoplasms / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D020413:3' Untranslated Regions; D043170:Collagen Type XVIII