Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.
Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.
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在北方北部人口中，肝素酶基因与胃癌的进展和预后相关的多态性和单倍型。
DOI：
10.1371/journal.pone.0030277
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Xu HM
中科院分区：
文献类型：
--
作者：
Li AL;Song YX;Wang ZN;Gao P;Miao Y;Zhu JL;Yue ZY;Xu HM
人乙酰肝素酶在肿瘤发生发展中起重要作用，乙酰肝素酶基因（HPSE）的单核苷酸多态性（SNP）已被证明与胃癌相关。本研究在中国北方大样本汉族人群中检测HPSE单核苷酸多态性或单倍型与胃癌易感性、临床病理参数和预后的关系。从404名患者的福尔马林固定、石蜡包埋的正常胃组织样本和404名健康对照者的血液中提取基因组DNA。采用基质辅助激光解吸/电离飞行时间质谱法对6个SNP进行基因分型。采用χ2检验和非条件Logistic回归分析胃癌的危险度，Log-rank检验和考克斯比例风险模型分析生存率，Kaplan-Meier法绘制生存曲线。两组的平均基因分型成功率均超过99%。在由rs 11099592和rs 4693608组成的区块中，单倍型CA在Borrmann 3型和4型组中的分布更大（P = 0.037），淋巴结转移数目更多的组（N3 vs N 0组，P = 0.046），并且与较差的生存相关（CG vs CA：HR = 0.645，95%CI：0.421-0.989，P = 0.044）。 此外，基因型rs 4693608 AA和rs 4364254 TT与生存率差相关（rs 4693608 AA，P =0.030，HR=1.527，95%CI：1.042-2.238; rs 4364254 TT，P= 0.013，HR =1.546，95%CI：1.096-2.181）。 单个SNPs或单倍型与胃癌风险之间没有相关性。在HPSE中发现了一个功能性单倍型，其中包括重要的SNP rs 4693608。HPSE中的SNPs在胃癌的进展和生存中起重要作用，可能成为判断预后和治疗价值的分子标志物。
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. 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. 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.
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影响因子：
3.9
作者：
Jaremko, M;Justenhoven, C;Brauch, H
通讯作者：
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影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
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作者：
Gilbert, Marcus T. P.;Sanchez, Juan J.;Worobey, Michael
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Worobey, Michael
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Taqman 基因分型测定可用于骨肉瘤患者的脱钙组织和石蜡包埋组织
影响因子：
3.2
作者：
Hagleitner, Melanie M.;Coenen, Marieke J. H.;Hoogerbrugge, Peter M.
通讯作者：
Hoogerbrugge, Peter M.