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

Cited 25 time in scopus
Metadata Downloads
Title
SERPINE1 intron polymorphisms affecting gene expression are associated with diffuse-type gastric cancer susceptibility
Author(s)
H Ju; B Lim; M Kim; S M Noh; W H Kim; C Ihm; B Y Choi; Yong Sung Kim; C Kang
Bibliographic Citation
Cancer, vol. 116, no. 18, pp. 4248-4255
Publication Year
2010
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.
Keyword
Clade EDiffuse-type gastric cancerDisease susceptibility associationInsertion/deletion polymorphismMember 1Plasminogen activator inhibitor type 1Serpin peptidase inhibitor 1Single nucleotide polymorphism
ISSN
0008-543X
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/cncr.25213
Type
Article
Appears in Collections:
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.