Association of heparanase gene (HPSE-1) single nucleotide polymorphisms with gastric cancer

Abstract

Background: Heparanase activity plays a decisive role in biological processes associated with remodeling of the extracellular matrix (e.g., cancer metastasis, angiogenesis, and inflammation). Heparanase gene overexpression has been associated with advanced stage and poor survival in several cancers. We investigated the potential association between single nucleotide polymorphisms (SNPs) of the HPSE-1 gene, tumor susceptibility, clinicopathological parameters, and survival with gastric cancer among the Han population in northern China. Methods: In this case - control study, there were 155 patients with gastric cancer and 204 healthy controls. The genotyping was performed using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) assay. Chi-square test was performed to exam differences of genotypes or alleles frequency between samples. The effect of various variables on outcome was investigated by multivariate analysis using the Cox proportional hazards model. Results: We identified four polymorphisms in the HPSE-1 gene. Polymorphisms in introns 2 and 3, exon8, and exon13 occurred at a minor allele frequency of ≥10%. There was an increase in frequency of individuals with a genotype that carried the intron3 (A), exon8 (A), exon13 (G) haplotype (AAG) in patients with gastric cancer compared with healthy individuals (P=0.0001; OR=7.467; 95% CI: 2.274-24.509). SNP rs11099592 variant genotypes AG/AA were associated with a Borrmann type classification (P=0.015; OR=0.182; 95% CI: 0.049-0.668) and invasion depth (P=0.020; OR=0.341; 95% CI: 0.134-0.866), whereas SNP rs4328905 AG genotype was correlated to Lauren diffuse grade (P=0.027; OR=0.419; 95% CI 0.191-0.917). SNP rs6856901 variant genotypes GC/CC were associated with a better tumor-related survival (P=0.028; OR=0.504; 95% CI: 0.273-0.930) compared with GG genotype. Conclusions: HPSE-1 polymorphisms may contribute to gastric tumor characteristics. SNP rs6856901 may be helpful in identifying clinical outcome of patients with gastric cancer. © 2010 Wiley-Liss, Inc.