A regulatory polymorphism at position -309 in PTPRCAP is associated with susceptibility to diffuse-type gastric cancer and gene expression

Cited 16 time in scopus
Metadata Downloads
Title
A regulatory polymorphism at position -309 in PTPRCAP is associated with susceptibility to diffuse-type gastric cancer and gene expression
Author(s)
H Ju; B Lim; M Kim; Yong Sung Kim; W H Kim; C Ihm; S M Noh; D S Han; H J Yu; B Y Choi; C Kang
Bibliographic Citation
Neoplasia, vol. 11, no. 12, pp. 1340-1347
Publication Year
2009
Abstract
PTPRCAP (CD45-AP) is a positive regulator of protein tyrosine phosphatase PTPRC (CD45), which activates Src family kinases implicated in tumorigenesis. Single-nucleotide polymorphism (SNP) rs869736 located at position -309 of the PTPRCAP promoter was associated with susceptibility to diffuse-type gastric cancer in the current case-control study. The minor-allele homozygote was significantly associated with a 2.5-fold increased susceptibility to diffusetype gastric cancer (P = .0021, n = 252), but not to intestinal-type (P = .30, n = 178), versus the major-allele homozygote, when comparing unrelated Korean patients with healthy controls (n = 406). Nine other SNPs were in nearly perfect linkage disequilibrium (r2 ≥ 0.97) with this SNP, exhibiting the same association, and spread out for 26 kb on chromosome 11q13.1 covering RPS6KB2, PTPRCAP, CORO1B, and GPR152. Among the four genes, however, only PTPRCAP expression was affected by haplotypes of the 10 SNPs. Endogenous transcript levels of PTPRCAP were linearly correlated with copy numbers (0, 1, and 2) of the risk-haplotype (P = .0060) in 12 lymphoblastoid cells derived from blood samples, but those of the other three genes were not. Furthermore, the cancer-risk, minor-allele T of rs869736 increased both promoter activity and specific nuclear protein-binding affinity than the nonrisk, major-allele G in luciferase reporter and electrophoretic mobility shift assays, respectively. Accordingly, the minor allele of rs869736 in the PTPRCAP promoter is associated with increased susceptibility to diffuse-type gastric cancer by increasing PTPRCAP expression, possibly leading to activation of the oncogenic Src family kinases.
ISSN
1522-8002
Publisher
Elsevier
DOI
http://dx.doi.org/10.1593/neo.91132
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.