SERPINE1 intron polymorphisms affecting gene expression are associated with diffuse-type gastric cancer susceptibility

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dc.contributor.authorH Ju-
dc.contributor.authorB Lim-
dc.contributor.authorM Kim-
dc.contributor.authorS M Noh-
dc.contributor.authorW H Kim-
dc.contributor.authorC Ihm-
dc.contributor.authorB Y Choi-
dc.contributor.authorYong Sung Kim-
dc.contributor.authorC Kang-
dc.date.accessioned2017-04-19T09:19:51Z-
dc.date.available2017-04-19T09:19:51Z-
dc.date.issued2010-
dc.identifier.issn0008543X-
dc.identifier.uri10.1002/cncr.25213ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/9766-
dc.description.abstractBACKGROUND: A primary inhibitor of plasminogen activators, SERPINE1 (serpin peptidase inhibitor 1, clade E, member 1, also known as plasminogen activator inhibitor type 1), is an important regulator in tumorigenesis and is highly expressed in many cancers. METHODS: Five tag single nucleotide polymorphisms (SNPs) and 1 insertion polymorphism within SERPINE1 were genotyped in 1101 unrelated Korean individuals (a case group of 612 patients with gastric cancer and a control group of 489 healthy individuals). Associations with susceptibility to diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer were assessed using multivariate logistic regression analyses adjusted for age and sex. Allelic differences in the contribution to gene expression were measured using luciferase assays. RESULTS: SNP c.1162+162C>T (rs2227692) in intron 7 was associated with susceptibility to DGC but not with susceptibility to intestinaltype gastric cancer.The minor allele-carrying genotypes C/Tand T/T had 1.6-fold greater odds of DGC than the C/C genotype (P=.00084). This SNP was linked to a repeat-number variation c.1162+604AAAG(11-17), a deletion (del) variation c.1162+664-1162+673del, and another SNP c.1162+859T>A (rs2070683) in intron 7 based on the sequencing of 5 patients and 5 controls.The risk haplotype of the 4 variations exhibited a 30% greater gene expression level than the nonrisk haplotype in luciferase reporter assays (P=.025). In contrast, DGC susceptibility was not associated with the c.-1969--1968insG polymorphism (rs1799768) in the promoter, commonly known as 4G/5G, in which the minor 5G allele is less active in transcription than the major 4G allele. CONCLUSIONS: An association between SERPINE1 and DGC susceptibility was observed with 4 correlated polymorphisms in intron 7 rather than the 4G/5G polymorphism in the promoter, although all polymorphisms affected gene expression.-
dc.publisherWiley-
dc.titleSERPINE1 intron polymorphisms affecting gene expression are associated with diffuse-type gastric cancer susceptibility-
dc.title.alternativeSERPINE1 intron polymorphisms affecting gene expression are associated with diffuse-type gastric cancer susceptibility-
dc.typeArticle-
dc.citation.titleCancer-
dc.citation.number18-
dc.citation.endPage4255-
dc.citation.startPage4248-
dc.citation.volume116-
dc.contributor.affiliatedAuthorYong Sung Kim-
dc.contributor.alternativeName주형석-
dc.contributor.alternativeName임병호-
dc.contributor.alternativeName김민진-
dc.contributor.alternativeName노승무-
dc.contributor.alternativeName김우호-
dc.contributor.alternativeName임춘화-
dc.contributor.alternativeName최보열-
dc.contributor.alternativeName김용성-
dc.contributor.alternativeName강창원-
dc.identifier.bibliographicCitationCancer, vol. 116, no. 18, pp. 4248-4255-
dc.identifier.doi10.1002/cncr.25213-
dc.subject.keywordClade E-
dc.subject.keywordDiffuse-type gastric cancer-
dc.subject.keywordDisease susceptibility association-
dc.subject.keywordInsertion/deletion polymorphism-
dc.subject.keywordMember 1-
dc.subject.keywordPlasminogen activator inhibitor type 1-
dc.subject.keywordSerpin peptidase inhibitor 1-
dc.subject.keywordSingle nucleotide polymorphism-
dc.subject.localClade E-
dc.subject.localDiffuse-type gastric cancer-
dc.subject.localDisease susceptibility association-
dc.subject.localInsertion/deletion polymorphism-
dc.subject.localMember 1-
dc.subject.localPlasminogen activator inhibitor type 1-
dc.subject.localSerpin peptidase inhibitor 1-
dc.subject.localSingle nucleotide polymorphism-
dc.subject.localSingle nucleotide polymorphism (SNP)-
dc.description.journalClassY-
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Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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