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肝素酶基因 (HPSE-1) 单核苷酸多态性与胃癌的关联。

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

机构信息

Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, China.

出版信息

J Surg Oncol. 2010 Jul 1;102(1):68-72. doi: 10.1002/jso.21584.

DOI:10.1002/jso.21584

PMID:20578081

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 >or=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.

摘要

背景

肝素酶活性在与细胞外基质重塑相关的生物学过程中起着决定性作用（例如癌症转移、血管生成和炎症）。肝素酶基因的过表达与几种癌症的晚期和预后不良有关。我们在中国北方汉族人群中研究了 HPSE-1 基因的单核苷酸多态性（SNP）与肿瘤易感性、临床病理参数和生存之间的潜在关联。

方法

在这项病例对照研究中，有 155 名胃癌患者和 204 名健康对照者。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析进行基因分型。使用卡方检验比较样本中基因型或等位基因频率的差异。使用 Cox 比例风险模型的多变量分析研究各种变量对结果的影响。

结果

我们在 HPSE-1 基因中发现了四个多态性。内含子 2 和 3、外显子 8 和外显子 13 的多态性在>或=10%的小等位基因频率下发生。与健康个体相比，胃癌患者携带内含子 3（A）、外显子 8（A）、外显子 13（G）单倍型（AAG）的个体基因型频率增加（P=0.0001；OR=7.467；95%CI：2.274-24.509）。SNP rs11099592 变体基因型 AG/AA 与 Borrmann 分型（P=0.015；OR=0.182；95%CI：0.049-0.668）和浸润深度（P=0.020；OR=0.341；95%CI：0.134-0.866）相关，而 SNP rs4328905 AG 基因型与 Lauren 弥漫性分级相关（P=0.027；OR=0.419；95%CI 0.191-0.917）。SNP rs6856901 变体基因型 GC/CC 与肿瘤相关生存率的改善相关（P=0.028；OR=0.504；95%CI：0.273-0.930）相比，GG 基因型。