Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to understand the molecular bases of gastric cancer progression, we have analyzed the differentially expressed genes in gastric cancer by SAGE. Four SAGE cDNA tag libraries were constructed from two sets of gastric cancer and normal tissues and 241,127 tags were obtained. By comparing the tags from cancer and normal tissues, 414 differentially expressed tags, representing 383 genes, were identified in cancer tissues (p </= 0.01). Of the 414 tags, 50 tags were previously unidentified and potentially novel genes. Although each gastric cancer tissue revealed more than 200 differentially expressed genes compared to the respective normal tissue, the number of genes with consistent regulation patterns in both cancer tissues was 51: 12 up-regulated and 39 down-regulated genes. The genes that showed consistent regulation patterns included well-known genes such as Trefoil factor 3, RegIV, gastric intrinsic factor, and lactotransferrin as well as a few novel candidates. Interestingly, the expression of several genes, such as osteoglycin, prostate stem cell antigen, and histone deacetylase 3, was variable in the two normal tissues but similar in the cancer tissues. The expression profiles of these genes in normal tissues, possibly due to genetic background, could greatly affect individual sensitivity to cancer development and/or progression. The genes identified in this study will provide useful target genes for diagnosis and molecular treatment of gastric cancer.
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PMID:Analysis of gene expression profiles of gastric normal and cancer tissues by SAGE. 1280 78

Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in PSCA (prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38-1.89, P = 1.11 x 10(-9)). The association was far less significant in intestinal-type gastric cancer. We found that PSCA is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity in vitro and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has r(2) = 0.995, D' = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56-2.33, P = 8.01 x 10(-11)). The polymorphism of the PSCA gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.
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PMID:Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer. 1848 30

A genome-wide association study on diffuse-type gastric cancer identified the PSCA gene, whose exact function in the gastric epithelium has been unknown. Immunohistochemical analysis revealed that PSCA is expressed in the region in which gastric epithelial stem cells and precursors are considered to reside. Moreover, the PSCA was downregulated in gastric cancer tissues, and its product showed a cell-growth inhibition activity in vitro. We also identified a functional SNP, the risk allele of which suppressed a promoter activity of the PSCA gene. These findings suggest that the PSCA may contribute to carcinogenesis through the cell-growth regulation of the gastric epithelial precursors. The summary statistics of the 2-stage genome scan is available from a database, GeMDBJ (http://gemdbj.nibio.go.jp/).
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PMID:[Genome-wide association study of gastric cancer and GeMDBJ database]. 1950 19

Genetic factors play important roles in pathogenesis of human cancer. A recent genome-wide association study (GWAS) linked two single nucleotide polymorphisms (SNPs) in prostate stem cell antigen (PSCA), rs2294008C>T and rs2976392G>A, to risk of diffuse-type of gastric cancer in Japanese and Korean populations. We hypothesized that these two SNPs are also associated with risk of gastric cancer in Chinese population. We examined genotypes and haplotypes of PSCA, rs2294008C/T and rs2976392G/A in 716 patients with cardia gastric carcinoma (CGC), 1020 patients with noncardia gastric carcinoma (NCGC), and 1020 controls. We found that individuals with at least one copy of the rs2294008T allele (CT or TT genotype) had an elevated risk for developing NCGC compared with those without this allele (OR = 1.35, 95% CI = 1.13-1.61). Individuals with at least one copy of the rs2976392A allele (GA or AA genotype) had nonsignificantly increased risk for NCGC compared with those without this allele (OR = 1.20, 95% CI = 1.01-1.43). Stratification analysis showed that the increased risk associated with the SNPs was restricted in female subjects. Moreover, the rs2294008T and rs2976392A allele carriers were predisposed to developing poorly differentiated and high stage NCGC at diagnosis. However, no such association was detected for CGC. In addition, we observed considerably lower allelic and genotype frequencies of these genetic variants in Chinese population compared with Japanese and Korean populations. These findings are in general consistent with previous GWAS and suggest that PSCA may play a role in the development of NCGC in Chinese population.
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PMID:Two genetic variants in prostate stem cell antigen and gastric cancer susceptibility in a Chinese population. 1955 73

A recent whole-genome association study identified a strong association between polymorphisms in the prostate stem cell antigen (PSCA) gene and stomach cancer risk. In this case-control study, we aimed to validate this association, and further to explore environmental factors possibly interacting with PSCA polymorphisms in 708 incident stomach cancer cases and 708 age-sex matched controls. The association between PSCA polymorphisms and Helicobacter pylori infection was also examined. We found that rs2294008 and rs2976392, which were strongly linked to each other (D' = 1.00), were significantly associated with stomach cancer risk. Per allele odds ratio for rs2994008 was 1.40 (95% confidence interval: 1.19-1.65; p = 3.7 x 10(-5)). We found significant interaction with a family history of stomach cancer in first-degree relatives (p-heterogeneity = 0.009). Similar to originally reported association, we found significant heterogeneity between diffuse and intestinal type (p-heterogeneity = 0.007). No association was seen between PSCA polymorphisms and H. pylori infection. In conclusion, PSCA polymorphisms are associated with stomach cancer risk in Japanese. A possible interaction with family history warrants further evaluation.
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PMID:Association of prostate stem cell antigen gene polymorphisms with the risk of stomach cancer in Japanese. 1958 81

Recently, two genome-wide association studies identified a significant association between the prostate stem cell antigen (PSCA) rs2294008 (C>T) polymorphism and risk of diffuse-type of gastric cancer in Asians and bladder cancer in Caucasians, respectively. PSCA has been reported highly expressed in bladder cancer and been considered as a useful marker for diagnosis and progression of bladder cancer. To determine whether rs2294008 polymorphism is associated with risk of bladder cancer in Chinese populations, we conducted a hospital-based case-control study of 581 cases and 580 controls. Sixteen normal bladder tissues adjacent to tumors were used to evaluate the functionality of this polymorphism. We genotyped the rs2294008 polymorphism and assessed its association with risk of bladder cancer and messenger RNA (mRNA) expression in normal bladder tissues. A significant increased risk of bladder cancer was found for rs2294008 CT/TT genotypes (adjusted odds ratio, 1.38; 95% confidence interval, 1.09-1.75) compared with the CC genotype. Furthermore, analysis of PSCA mRNA expression identified a clear correlation of rs2294008 with expression levels of PSCA mRNA. These results indicated that the rs2294008 polymorphism of PSCA gene may play a role in bladder cancer carcinogenesis and it could be served as a biomarker for genetic susceptibility to bladder cancer in Chinese populations.
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PMID:Genetic variation in PSCA and bladder cancer susceptibility in a Chinese population. 2008 43

Prostate stem cell antigen (PSCA), a member of the LY-6/Thy-1 family of glycosylphosphatidylinositol-anchored cell surface proteins, is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Two single nucleotide polymorphisms (SNPs) (rs2976392 and rs2294008) in the PSCA gene were recently identified as the susceptibility loci of gastric cancer, especially in diffuse type. Therefore, this study was to investigate whether these 2 SNPs were associated with the risk of gastric cancer in Chinese population. We genotyped rs2976392 and rs2294008 in PSCA in a case-control study including 1,053 incident gastric cancer patients and 1,100 cancer-free controls in a high-risk Chinese population. We found that variant genotypes of rs2976392 (GA/AA) were associated with a significantly 37% increased risk of gastric cancer (adjusted OR =1.37, 95% CI = 1.15-1.62), compared with variant homozygote GG, and the associations were all consistently significant in both intestinal and diffuse subtypes, and among different subgroups stratified by age, sex, drinking or smoking status. Interestingly, a significant multiplicative interaction between rs2976392 (GA/AA) and alcohol drinking was detected on the development of intestinal-type gastric cancer (p = 0.009). However, rs2294008 variant genotypes (CT/TT) were associated with a nonsignificant increased risk of gastric cancer (adjusted OR = 1.14, 95% CI = 0.96-1.36). A small meta-analysis including 5 case-control studies showed undoubtedly associations between PSCA rs2294008 and rs2976392 and gastric cancer risk (OR = 1.83, 95% CI: 1.29-2.60 and OR = 1.84, 95% CI: 1.33-2.56, respectively). These findings provide further evidence supporting that the genetic variants of PSCA gene may contribute to the gastric carcinogenesis.
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PMID:Genetic variation of PSCA gene is associated with the risk of both diffuse- and intestinal-type gastric cancer in a Chinese population. 2013 15

Genetic factors are known to be important in the development of gastric cancer (GC). Prostate stem cell antigen (PSCA) has been shown to be expressed in diffuse-type GC, and PSCA variation is associated with susceptibility to diffuse-type GC in Japanese and Korean populations. The aim of this study was to investigate the association between PSCA gene polymorphisms and GC in a Tibetan population. We analyzed single-nucleotide polymorphisms of the PSCA gene in 196 patients with GC and 246 controls in a Tibetan population, using a polymerase chain reaction/ligase detection reaction test. The rs2294008 C/T polymorphism of the PSCA gene was significantly associated with the susceptibility to GC. The CT genotype was associated with a significantly higher risk of GC when compared with the CC genotype (odds ratio [OR] = 1.50; 95% confidence interval [CI], 1.01-2.23). Patients carrying the T allele had a significantly higher risk for developing GC compared with individuals carrying the C allele (OR = 1.34; 95% CI, 1.00-1.79). Haplotype analyses showed that CA haplotype was associated with a significantly decreased risk of GC when compared with the CG haplotype (OR = 0.47; 95% CI, 0.24-0.93). Our data indicate that PSCA gene polymorphisms may be associated with GC in Tibetans.
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PMID:Association and haplotype analysis of prostate stem cell antigen with gastric cancer in Tibetans. 2023 Feb 93

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. Although PSCA is thought to be involved in intracellular signaling, much remains unknown about its physiological function and regulatory mechanism in normal and cancer cells. It is up-regulated in several major cancers including prostate, bladder, and pancreatic cancers. The expression of PSCA is positively correlated with advanced clinical stage and metastasis in prostate cancers and is also associated with malignant progression of premalignant prostate lesions. Therefore, PSCA has been proposed as a biomarker of diagnosis and prognosis, as well as a target of therapy for these cancers. In addition, PSCA has also shown clinical potential in immunotherapy as a prostate-specific antigen, which, when presented by dendritic cells, may elicit strong tumor-specific immunity. In contrast, PSCA is down-regulated in esophageal and gastric cancer and may have a tumor-suppressing function in the gastric epithelium. Recent exciting findings that genetic variations of PSCA conferred increased risks of gastric cancer and bladder cancer have opened up a new avenue of research about the pathological function of PSCA. PSCA seems to be a Jekyll and Hyde molecule that plays differential roles, tumor promoting or suppressing, depending on the cellular context.
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PMID:Prostate stem cell antigen: a Jekyll and Hyde molecule? 2050 18

The power of an SNP-based genome-wide association study (GWAS) was first demonstrated in Japan using the JSNP database and is currently a major strategy adopted around the world for a number of common diseases including cancers. The hypothesis-free strategy can lead us to a novel hypothesis for carcinogenesis and may contribute to identifying a high risk group for research and, in the future, practice of personalized prevention. We performed a GWAS on diffuse-type gastric cancer and identified a significant association with SNPs in the PSCA (prostate stem cell antigen) gene. The association was validated by a Korean gastric case-control analysis. The PSCA protein is expressed predominantly in the stem cell/precursor-rich region of the gastric epithelium, which is considered as the origin of diffuse-type gastric cancer, and showed tumor suppressor-like characteristics. Individuals with a low PSCA promoter activity are susceptible to diffuse-type gastric cancer. By contrast, the polymorphism does not significantly predispose to intestinal-type gastric cancer, congruous to the hypothesis of the two distinct carcinogenesis pathways for the two major types of gastric cancer. In addition to publication on a specific gene, the sharing of GWAS data through a database on the web is expected to accelerate validation and discovery by other investigators. GeMDBJ (Genome Medicine Database of Japan), started in 2005 in Japan, is one of such attempts. Moreover, the advent of "next generation" sequencers may herald a new era in which the poorly explored domains of the genetic architecture of disease susceptibility may be unveiled.
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PMID:Genome-wide germline analyses on cancer susceptibility and GeMDBJ database: Gastric cancer as an example. 2050 24


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