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Impact of PSCA variation on gastric ulcer susceptibility.

ABSTRACT: Peptic ulcer is one of the most common gastrointestinal disorders with complex etiology. Recently we conducted the genome wide association study for duodenal ulcer and identified disease susceptibility variations at two genetic loci corresponding to the Prostate stem cell antigen (PSCA) gene and the ABO blood group (ABO) gene. Here we investigated the association of these variations with gastric ulcer in two Japanese case-control sample sets, a total of 4,291 gastric ulcer cases and 22,665 controls. As a result, a C-allele of rs2294008 at PSCA increased the risk of gastric ulcer with odds ratio (OR) of 1.13 (P value of 5.85×10(-7)) in an additive model. On the other hand, SNP rs505922 on ABO exhibited inconsistent result between two cohorts. Our finding implies presence of the common genetic variant in the pathogenesis of gastric and duodenal ulcers.

SUBMITTER: Tanikawa C

PROVIDER: S-EPMC3660579 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Impact of PSCA variation on gastric ulcer susceptibility.

Tanikawa Chizu C Matsuo Keitaro K Kubo Michiaki M Takahashi Atsushi A Ito Hidemi H Tanaka Hideo H Yatabe Yasushi Y Yamao Kenji K Kamatani Naoyuki N Tajima Kazuo K Nakamura Yusuke Y Matsuda Koichi K

PloS one 20130521 5

Peptic ulcer is one of the most common gastrointestinal disorders with complex etiology. Recently we conducted the genome wide association study for duodenal ulcer and identified disease susceptibility variations at two genetic loci corresponding to the Prostate stem cell antigen (PSCA) gene and the ABO blood group (ABO) gene. Here we investigated the association of these variations with gastric ulcer in two Japanese case-control sample sets, a total of 4,291 gastric ulcer cases and 22,665 contr ...[more]

PMID: 23704932

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Project description:IntroductionGenetic factors play an important role in the development of gastric cancer (GC), a prevalent malignancy in Central Asia. Recent studies have shown that single-nucleotide polymorphisms (SNPs) in several genes are associated with increased GC risk, indicating that genetic variation contributes to gastric carcinogenesis. Located on chromosome 8q24.2, the prostate stem cell antigen (PSCA) gene encodes a 123-amino acid glycoprotein related to the cell-proliferation inhibition and cell-death induction activity. SNPs in PSCA gene have been found to be associated with gastric cancer risk in a genome-wide association study, but results were not conclusive. This study aimed to investigate the association between two polymorphic variants of PSCA gene (rs2294008 and rs9297976) and the susceptibility to gastric cancer in Uzbekistan.MethodsTwo hundred sixty eight patients with gastric cancer and a control group of 248 healthy individuals were included in this study. DNA samples isolated from these groups were genotyped using PCR-RFLP method. Comparative analysis of resulting genotypes showed a statistically significant association between CT genotype and gastric cancer (p=0.03, additive model of inheritance, Cochran-Armitage trend test).ResultsComparative analysis of the distribution of genotypes of rs2976392 polymorphism did not show a statistically significant difference; however, analysis of the distribution of the rs2976392 genotypes in a subgroup of young women revealed a statistically significant (p = 0.04, additive model of inheritance, Cochran-Armitage trend test) increase in the incidence of AA (38%) and AG (56%) genotypes in patients with GC, compared to the controls (20% and 40%).ConclusionOur findings support that PSCA rs2294008 and rs9297976 polymorphism may contribute to the susceptibility to gastric cancer. Genotyping of these polymorphisms can potentially be recommended as one of the criteria for identification of high risk groups for gastric cancer development in Uzbekistan.

Dataset Information

Impact of PSCA variation on gastric ulcer susceptibility.

Publications

Impact of PSCA variation on gastric ulcer susceptibility.

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