title: Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.
abstract: BACKGROUND
  Human heparanase plays an important role in cancer development and single nucleotide polymorphisms (SNPs) in the heparanase gene (HPSE) have been shown to be correlated with gastric cancer. The present study examined the associations between individual SNPs or haplotypes in HPSE and susceptibility, clinicopathological parameters and prognosis of gastric cancer in a large sample of the Han population in northern China.
  
  
  RESULTS
  Genomic DNA was extracted from formalin-fixed, paraffin-embedded normal gastric tissue samples from 404 patients and from blood from 404 healthy controls. Six SNPs were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A chi-square (χ2) test and unconditional logistic regression were used to analyze the risk of gastric cancer; a Log-rank test and Cox proportional hazards model were used to produce survival analysis and a Kaplan-Meier method was used to map survival curves. The mean genotyping success rates were more than 99% in both groups. Haplotype CA in the block composed of rs11099592 and rs4693608 had a greater distribution in the group of Borrmann types 3 and 4 (P = 0.037), the group of a greater number of lymph node metastases (N3 vs N0 group, P = 0.046), and moreover was correlated to poor survival (CG vs CA: HR = 0.645, 95%CI: 0.421-0.989, P = 0.044). In addition, genotypes rs4693608 AA and rs4364254 TT were associated with poor survival (P = 0.030, HR = 1.527, 95%CI: 1.042-2.238 for rs4693608 AA; P = 0.013, HR = 1.546, 95%CI: 1.096-2.181 for rs4364254 TT). There were no correlations between individual SNPs or haplotypes and gastric cancer risk.
  
  
  CONCLUSIONS
  A functional haplotype in HPSE was found, which included the important SNP rs4693608. SNPs in HPSE play an important role in gastric cancer progression and survival, and perhaps may be a molecular marker for prognosis and treatment values.
authors.affiliation: Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Ai-Lin
authors.initials: AL
authors.lastname: Li
authors.forename: Yong-Xi
authors.initials: YX
authors.lastname: Song
authors.forename: Zhen-Ning
authors.initials: ZN
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Miao
authors.forename: Jin-Liang
authors.initials: JL
authors.lastname: Zhu
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Yue
authors.forename: Hui-Mian
authors.initials: HM
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005966:Glucuronidase / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D000099175:Heparanase