Dataset Information

Programmed death-1 (PD-1) polymorphism is associated with gastric cardia adenocarcinoma.

ABSTRACT: Polymorphisms in gene encoding programmed death-1 (PD-1) were suggested to be associated with the risk of multiple cancers. To the best of our knowledge, no investigation has been carried out for gastric cardia adenocarcinoma (GCA) and PD-1 polymorphisms. Thus, we studied PD-1 rs10204525 A>G, rs7421861 T>C and rs2227982 C>T single nucleotide polymorphisms (SNPs) in 330 GCA cases and 608 cancer-free controls. Genotypes of PD-1 SNPs were determined by ligation detection reaction (LDR) assays. The distributions of the allele and genotype were not statistically significant in two groups for the three PD-1 SNPs. However, in stratified analyses by various characteristics (eg., age, sex, smoking condition and alcohol consumption status), we found a significantly increased risk of GCA associated with the PD-1 rs2227982 C>T polymorphism was evident among ever drinking cases (TT vs. CC: adjusted OR = 2.53, 95% CI = 1.11-5.79, P = 0.028; TT+CT vs. CC: adjusted OR = 2.04, 95% CI = 1.01-4.13, P = 0.047). For the other SNPs, in stratified analyses, no correlation between the SNPs and susceptibility of GCA was observed. In conclusion, our results highlight that rs2227982 C>T polymorphism in PD-1 gene may contribute to the risk of GCA.

SUBMITTER: Tang W

PROVIDER: S-EPMC4509319 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Programmed death-1 (PD-1) polymorphism is associated with gastric cardia adenocarcinoma.

Tang Weifeng W Chen Yu Y Chen Shuchen S Sun Bin B Gu Haiyong H Kang Mingqiang M

International journal of clinical and experimental medicine 20150515 5

Polymorphisms in gene encoding programmed death-1 (PD-1) were suggested to be associated with the risk of multiple cancers. To the best of our knowledge, no investigation has been carried out for gastric cardia adenocarcinoma (GCA) and PD-1 polymorphisms. Thus, we studied PD-1 rs10204525 A>G, rs7421861 T>C and rs2227982 C>T single nucleotide polymorphisms (SNPs) in 330 GCA cases and 608 cancer-free controls. Genotypes of PD-1 SNPs were determined by ligation detection reaction (LDR) assays. The ...[more]

PMID: 26221374

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Project description:In the present study, gene expression profiles were analyzed to identify the molecular mechanisms underlying gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA). A gene expression dataset (accession number GSE29272) was downloaded from Gene Expression Omnibus, and consisted of 62 GCA samples and 62 normal controls, as well as 72 GNCA samples and 72 normal controls. The two groups of differentially-expressed genes (DEGs) were compared to obtain common and unique DEGs. A differential analysis was performed using the Linear Models for Microarray Data package in R. Functional enrichment analysis was conducted for the DEGs using the Database for Annotation, Visualization and Integrated Discovery. Protein-protein interaction (PPI) networks were constructed for the DEGs with information from the Search Tool for the Retrieval of Interacting Genes. Subnetworks were extracted from the whole network with Cytoscape. Compared with the control, 284 and 268 genes were differentially-expressed in GCA and GNCA, respectively, of which 194 DEGs were common between GCA and GNCA. Common DEGs [e.g., claudin (CLDN)7, CLDN4 and CLDN3] were associated with cell adhesion and digestion. GCA-unique DEGs [e.g., MAD1 mitotic arrest deficient like 1, cyclin (CCN)B1, CCNB2 and CCNE1] were associated with the cell cycle and the regulation of cell proliferation, while GNCA-unique DEGs (e.g., GATA binding protein 6 and hyaluronoglucosaminidase 1) were implicated in cell death. A PPI network with 141 nodes and 446 edges were obtained, from which two subnetworks were extracted. Genes [e.g., fibronectin 1, collagen type I ?2 chain (COL1A2) and COL1A1] from the two subnetworks were implicated in extracellular matrix organization. These common DEGs could advance our understanding of the etiology of gastric cancer, while the unique DEGs in GCA and GNCA could better define the properties of specific cancers and provide potential biomarkers for diagnosis, prognosis or therapy.

Project description:Recent decades have seen an alarming increase in the incidence of cardia gastric adenocarcinoma (CGA) while noncardia gastric adenocarcinoma (NCGA) has decreased. In 2012, 260 000 CGA cases (age-standardised rate (ASR); 3.3/100 000) and 691 000 NCGA cases (ASR; 8.8/100 000) were reported worldwide. Compared with women, men had greater rates for both the subsites, especially for CGA. Recently, four molecular subtypes of GC have been proposed by the Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG); however, these classifications do not take into account predisposing germline variants and their possible interaction with somatic alterations in carcinogenesis. The etiology of adenocarcinoma of the cardia and the gastroesophageal junction (GEJ) is not known. It is thought that CGA is distinct from adenocarcinomas located in the esophagus or distal stomach, both epidemiologically and biologically. Moreover, CGA is often identified in the advanced stage having a poor prognosis. Therefore, understanding the risk and the role of predisposing factors in etiology of CGA can inform clinical practice and counseling for risk reduction. In this paper, we showed that GC family history, lifestyle, demographics, gastroesophageal reflux disease, Helicobacter pylori infection, and multiple genetic and epigenetic risk factors as well as several predisposing conditions may underlie susceptibility to CGA. However, several genome-wide association studies (GWASs) should be conducted to identify novel high-penetrance genes and pathways as well as causal germline variants predisposing to CGA. They must include different ethnic groups, especially from high-incidence countries for CGA, because some risk loci are ancestry-specific. In parallel, statistical methods can be developed to identify cancer predisposition genes (CPGs) from tumor sequencing data. It is also necessary to find novel long noncoding RNAs related to the risk of CGA. Taken altogether, new cancer risk prediction models, including all genetic and nongenetic factors influencing risk, should be developed to facilitate risk assessment, disease prevention, and early diagnosis and intervention of CGA in the future.

Dataset Information

Programmed death-1 (PD-1) polymorphism is associated with gastric cardia adenocarcinoma.

Publications

Programmed death-1 (PD-1) polymorphism is associated with gastric cardia adenocarcinoma.

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