Journal
PLOS ONE
Volume 7, Issue 3, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0033855
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Funding
- National Basic Research Program of China (973 Program) [2012CB519005]
- Science Fund for Creative Research Groups [31021091]
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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.
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