Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.

<h4>Background</h4>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 haplotyp...

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Autores principales:	Ai-Lin Li, Yong-Xi Song, Zhen-Ning Wang, Peng Gao, Yuan Miao, Jin-Liang Zhu, Zhen-Yu Yue, Hui-Mian Xu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/202a7ff781a0411eb039fedcd90655c2
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spelling	oai:doaj.org-article:202a7ff781a0411eb039fedcd90655c22021-11-18T07:29:44ZPolymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.1932-620310.1371/journal.pone.0030277https://doaj.org/article/202a7ff781a0411eb039fedcd90655c22012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22276173/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Ai-Lin LiYong-Xi SongZhen-Ning WangPeng GaoYuan MiaoJin-Liang ZhuZhen-Yu YueHui-Mian XuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e30277 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ai-Lin Li Yong-Xi Song Zhen-Ning Wang Peng Gao Yuan Miao Jin-Liang Zhu Zhen-Yu Yue Hui-Mian Xu Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.
format	article
author	Ai-Lin Li Yong-Xi Song Zhen-Ning Wang Peng Gao Yuan Miao Jin-Liang Zhu Zhen-Yu Yue Hui-Mian Xu
author_facet	Ai-Lin Li Yong-Xi Song Zhen-Ning Wang Peng Gao Yuan Miao Jin-Liang Zhu Zhen-Yu Yue Hui-Mian Xu
author_sort	Ai-Lin Li
title	Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.
title_short	Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.
title_full	Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.
title_fullStr	Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.
title_full_unstemmed	Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.
title_sort	polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern chinese population.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/202a7ff781a0411eb039fedcd90655c2
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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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