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Title 

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

Authors 

H JuB LimM KimS M NohW H KimC IhmB Y ChoiYong Sung KimC Kang

Publisher 

Wiley-Blackwell

Issue Date 

2010

Citation 

Cancer, vol. 116, no. 18, pp. 4248-4255

Keywords 

Clade EDiffuse-type gastric cancerDisease susceptibility associationInsertion/deletion polymorphismMember 1Plasminogen activator inhibitor type 1Serpin peptidase inhibitor 1Single nucleotide polymorphism

Abstract 

BACKGROUND: 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.

ISSN 

0008-543X

Link 

http://dx.doi.org/10.1002/cncr.25213

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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