Abstract
Heparanase activity is involved in cancer growth and development in humans and single nucleotide polymorphisms (SNPs) in the heparanase gene (HPSE) have been shown to be associated with tumors. In this study, we investigated whether SNPs in HPSE were a risk factor for hepatocellular carcinoma (HCC) by undertaking a comprehensive haplotype-tagging, case-control study. For this, six haplotype-tagging SNPs (htSNPs) in HPSE were genotyped in 400 HCC patients and 480 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A log-additive model revealed significant correlations between the HPSE polymorphisms rs12331678 and rs12503843 and the risk of HCC in the overall samples (p = 0.0046 and p = 0.0055). When the analysis was stratified based on hepatitis B virus (HBV) carrier status, significant interactions between rs12331678 and rs12503843 and HBV were observed. Conditional logistic regression analysis for the independent effect of one significant SNP suggested that rs12331678 or rs12503843 contributed an independent effect to the significant association with the risk of HCC, respectively. Our findings suggest that the SNPs rs12331678 and rs12503843 are HCC risk factors, although the potential functional roles of these two SNPs remain to be fully elucidated.
Highlights
Human hepatocellular carcinoma (HCC), one of the most common tumors in the world, has a high incidence in China, Southeast Asia and sub-Saharan Africa, but a low incidence in the United States and Europe (Ferlay et al, 2010)
Various studies have examined the clinical significance of heparanase in HCC patients using immunohistochemistry, in situ hybridization, RT-PCR and real timePCR, western blotting and tissue microarrays (TMAs), with the general conclusion being that heparanase is upregulated in HCC (El-Assal et al, 2001; Xiao et al, 2003; Chen et al, 2004; Liu et al, 2005; Chen et al, 2008)
Significant correlations were found between the single nucleotide polymorphisms (SNPs) rs12331678 and rs12503843 and the risk of HCC in the overall samples in the log-additive model
Summary
Human hepatocellular carcinoma (HCC), one of the most common tumors in the world, has a high incidence in China, Southeast Asia and sub-Saharan Africa, but a low incidence in the United States and Europe (Ferlay et al, 2010). Down-regulating heparanase expression using either antisense oligodeoxynucleotides or RNA interference significantly inhibits the invasiveness, metastasis and angiogenesis of human HCC SMMC7721 cells in vitro and in vivo (Zhang et al, 2007). Two anti-heparanase antibodies (multiple antigenic peptides MAP1 and MAP2) can effectively inhibit the heparanase activity of HCCLM6 liver cancer cells, thereby influencing their invasive capacity (Yang et al, 2009). Together, these findings indicate that heparanase plays a vital role in HCC metastasis and tumor growth
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