Multiple studies have investigated the association of gene variant of Deleted in colorectal carcinoma (DCC) and Prostate Stem cell antigen (PSCA) with various cancer susceptibility; however, the results are discrepant. Since SNPs are emerging as promising biomarker of cancer susceptibility, here, we aimed to execute a meta-analysis of DCC (rs714 A > G) and PSCA (rs2294008 C > T, rs2976392 G > A) polymorphism to demonstrate the more accurate strength of these associations. We followed a rigorous inclusion/exclusion criteria and calculated the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Overall, the pooled analysis showed that the DCC rs714 conferred increased risk of cancer only in Asians (AA vs. GG: OR = 1.86, p ≤ 0.0001; AG vs. GG: OR = 1.43, p = 0.005; GA + AA vs. GG: OR = 1.66, p ≤ 0.0001; AA vs. GG + GA; OR = 1.52, p ≤ 0.004, A vs. G allele: OR = 1.41, p ≤ 0.0001). PSCA rs2294008 was associated with increased overall cancer risk (TT vs. CC: OR = 1.28, p = 0.002; CT vs. CC: OR = 1.21, p ≤ 0.0001; CT + TT vs. CC: OR = 1.24, p ≤ 0.0001; TT vs. CC + CT; OR = 1.17, p ≤ 0.005, T vs. C allele: OR = 1.16, p ≤ 0.0001); however, in stratified analysis this association was limited only to gastric and bladder cancer and the strength was more prominent in Asians. In contrast, the PSCA rs2976392 SNP did not modulate the cancer risk. Therefore, we concluded that rs714 and rs2294008 polymorphism may represent a potential genetic biomarker for cancer risk in Asians and gastric as well as bladder cancer, respectively. However, since our study is limited to Asians and cancer types, further larger studies involving other cancers and/or population, gene-environment interactions and the mechanism of DCC and PSCA gene deregulation are desired to define the role of genotype with overall cancer risk.

Impact of DCC (rs714) and PSCA (rs2294008 and rs2976392) Gene Polymorphism in Modulating Cancer Risk in Asian Population.

Previous studies have investigated the relationships between PSCA rs2294008 C>T and rs2976392 G>A polymorphisms and cancer susceptibility. However, the available findings remained inconsistent and even controversial. Thus, the aim of this meta-analysis was performed to clarify such associations. The online databases PubMed, EMBASE and Web of Science searched for relevant studies, covering all the papers published until September 1st, 2016. Data were pooled by odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of such associations. Then, trial sequential analysis was performed to estimate whether the evidence of the results was firm. Overall, a significant increased risk of cancer was associated with PSCA rs2294008 C>T and rs2976392 G>A polymorphisms. For the PSCA rs2294008 polymorphism, when stratified by type of cancer, the results were significant especially in gastric cancer and bladder cancer. Moreover, in the subgroup analysis by ethnicity, significant results were detected in both Asian and Caucasian populations. Similarly, for the PSCA rs2976392 polymorphism, the stratification analyses by type of cancer showed that the results were significant only in gastric cancer. In addition, the stratification analyses by ethnicity detected that this polymorphism increased cancer risk only in Asian populations. Then, trial sequential analyses demonstrated that the results of the meta-analysis were based on sufficient evidence. Therefore, this meta-analysis suggested that the PSCA rs2294008 C>T and rs2976392 G>A polymorphisms might be associated with cancer susceptibility, which might act as a potential predicted biomarker for genetic susceptibility to cancer, especially in gastric cancer and bladd er cancer.

/pdf/association-between-psca-gene-polymorphisms-and-the-risk-of-u3ecxifm0i.pdf

Association between PSCA gene polymorphisms and the risk of cancer: an updated meta-analysis and trial sequential analysis

The reported risk susceptibility between phospholipase C epsilon 1 (PLCE1) polymorphisms and esophageal cancer (EC) and gastric cancer (GC) remained inconsistent and controversial, especially on variants other than rs2274223. The relationship between PLCE1 polymorphisms and gene expression is also unclear. Here we conducted a case-control study from northwest China, genotyped seven tag single nucleotide polymorphisms (SNPs) in PLCE1 with multiplexed SNP MassARRAY assay. Stratified analysis was carried out and PLCE1 expression was evaluated in specified groups with the method of qRT-PCR and immunohistochemistry. Results showed that the minor alleles of rs3765524, rs2274223, and rs10509670 were associated with increased risk of EC and GC. Linkage disequilibrium analysis revealed protective haplotypes of CCAAGTC and CCAA. By stratification, a more significant association was found in subgroups of male, age ≥ 54, tumor stages of I-II and tumor size ≤ 5 cm, EC and cardia cancer (CC) of stomach, and moderate to well differentiated squamous carcinoma. In addition, a significant association for rs3765524 with noncardia cancer (NCC) and adenocarcinoma which is predominant in China was also observed. Further expression analysis identified that PLCE1 was downregulated in NCC tissues comparing to their adjacent noncancerous tissues, and its protein expression was higher in genotype rs3765524 CT/TT than in rs3765524 CC. In summary, our study suggests that PLCE1 polymorphisms may affect its gene expression and are associated with not only EC and CC, but also, to some extent, NCC risk in this study population.

/pdf/plce1-polymorphisms-and-risk-of-esophageal-and-gastric-50d1xho5ho.pdf

PLCE1 Polymorphisms and Risk of Esophageal and Gastric Cancer in a Northwestern Chinese Population

This study was to evaluate the associations of dietary intake of total and specific phytosterols and risk of esophageal squamous cell carcinoma (ESCC) and to explore their joint effects with PLCE1 rs2274223 polymorphisms. A population-based case–control study was conducted in a Chinese rural population and 856 eligible incident ESCC cases and 856 controls were included. A validated food frequency questionnaire was used to collect dietary consumption and PLCE1 rs2274223 polymorphisms were genotyped. Unadjusted and adjusted odds ratios (ORs) with 95% confidence interval (CI) were assessed via logistic regression model. When comparing the highest with lowest intake quartiles, β-sitosterol, campesterol, stigmasterol, β-sitostanol, campestanol, and total phytosterols were all associated with a decreased risk of ESCC, with adjusted ORs being 0.32 (95% CI 0.20–0.48), 0.18 (95% CI 0.11–0.27), 0.45 (95% CI 0.29–0.70), 0.13 (95% CI 0.08–0.20), 0.14 (95% CI 0.09–0.22) and 0.28 (95% CI 0.18–0.43), respectively. An exposure—response relationship was also observed for both total and five specific phytosterols (all P for trend < 0.001). In comparison to rs2274223 AA genotype, both GA genotype (OR: 1.47, 95% CI 1.16–1.85) and GG genotype (OR: 2.13, 95% CI 1.20–3.84) were associated with an increased risk of ESCC. However, no interaction was observed between total/specific phytosterols intake and rs2274223 polymorphisms. Higher dietary intake of total and five specific phytosterols was associated with a lower risk of ESCC, and the risk of ESCC increased with the increment of rs2274223 G allele. The negative association between phytosterols and ESCC risk was not modified by rs2274223 polymorphisms. Foods or supplements rich in phytosterols are a promising source for chemoprevention of ESCC, and still, clinical trials will be required in any specific case.

Independent and opposing associations of dietary phytosterols intake and PLCE1 rs2274223 polymorphisms on esophageal squamous cell carcinoma risk

Phospholipase C epsilon 1 (PLCE1) and the competing endogenous RNA (ceRNA) network are crucial for tumorigenesis and the progression of esophageal squamous cell carcinoma (ESCC). However, whether PLCE1 can regulate the ceRNA network in ESCC has not been clarified. In the present study, we aimed to identify the PLCE1‑regulated ceRNA network and further elucidate the regulatory mechanisms by which ESCC is promoted. Microarray analysis was used to identify differentially expressed lncRNAs (DELs) and differentially expressed genes (DEGs) from three pairs of samples of PLCE‑silenced Eca109 and control Eca109 cells. Next, the ceRNA regulatory network was established and visualized in Cytoscape, and functional enrichment analysis was performed to analyze DEGs from ceRNAs. Protein‑protein interaction (PPI) networks among the DEGs were established by the STRING database to screen hub genes. Kaplan‑Meier survival analysis was used to validate hub genes. Finally, PLCE1‑related hub gene/lncRNA/miRNA axes were also constructed based on the ceRNA network. A total of 105 DELs and 346 DEGs were found to be dysregulated in the microarray data (|log2FC| >1.5, adjusted P<0.05). We constructed a PLCE1‑regulated ceRNA network that incorporated 12 lncRNAs, 43 miRNAs, and 169 mRNAs. Functional enrichment analysis indicated that the DEGs might be associated with ESCC onset and development. A PPI network was established, and 9 hub genes [WD and tetratricopeptide repeats 1 (WDTC1), heat shock protein family A (Hsp70) member 5 (HSPA5), N‑ethylmaleimide sensitive factor, vesicle fusing ATPase (NSF), fibroblast growth factor 2 (FGF2), cyclin dependent kinase inhibitor 1A (CDKN1A or P21), bone morphogenetic protein 2 (BMP2), complement C3 (C3), GM2 ganglioside activator (GM2A) and discs large MAGUK scaffold protein 4 (DLG4)] were determined from the network. Kaplan‑Meier survival analysis validated four hub genes (BMP2, CDKN1A, GM2A, and DLG4) that were treated as prognostic factors. Ultimately, hub gene/lncRNA/miRNA subnetworks were obtained based on the 4 hub genes, 13 DEmiRNAs, and 10 DELs. In conclusion, the PLCE1‑regulated ceRNA contributes to the onset and progression of ESCC and the underlying molecular mechanisms may provide insights into personalized prognosis and new therapies for ESCC patients.

/pdf/identification-of-a-plce1-regulated-competing-endogenous-rna-s8rtlfa5fc.pdf

Identification of a PLCE1‑regulated competing endogenous RNA regulatory network for esophageal squamous cell carcinoma

Gastric adenocarcinoma (GAC) imposes a considerable health burden around the world. Gene variation in prostate stem cell antigen gene (PSCA) has been identified to be associated with GAC risk, while the results showed regional variation. To explore the influence of PSCA gene variation on its expression and GAC risk in the Northwest Chinese population, four single nucleotide polymorphisms (SNPs) of PSCA were genotyped in 476 GAC cases and 481 controls using MassARRAY system. Two SNPs of rs2294008 (C>T) and rs2976392 (G>A) were identified to be associated with GAC risk. rs2294008, rs2976392 and rs10216533 made up two statistically significant haplotypes (Hap-CGG and Hap-TAG). Additionally, PSCA expression was analyzed by quantitative real time PCR, immunohistochemistry and tissue microarray. The results showed that PSCA expression was decreased in GAC tissues compared with adjacent normal tissues. For normal tissues, PSCA expression was higher with Hap-TA than that with Hap-CG. For GAC tissues, the differentiation degree of Hap-TA was higher than that of Hap-CG. The expression distribution of PSCA in multiple human organs showed disparity. These results suggest that PSCA gene variation has a potential effect on its expression and GAC risk in the Northwest Chinese population.

The Influence of PSCA Gene Variation on Its Expression and Gastric Adenocarcinoma Susceptibility in the Northwest Chinese Population

Gastric adenocarcinoma (GAC) imposes a considerable health burden around the world. Gene variation in prostate stem cell antigen gene (PSCA) has been identified to be associated with GAC risk, while the results showed regional variation. To explore the influence of PSCA gene variation on its expression and GAC risk in the Northwest Chinese population, four single nucleotide polymorphisms (SNPs) of PSCA were genotyped in 476 GAC cases and 481 controls using MassARRAY system. Two SNPs of rs2294008 (C>T) and rs2976392 (G>A) were identified to be associated with GAC risk. rs2294008, rs2976392 and rs10216533 made up two statistically significant haplotypes (Hap-CGG and

The Influence of PSCA Gene Variation on Its Expression and Gastric Adenocarcinoma Susceptibility in the Northwest

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The Influence of PSCA Gene Variation on Its Expression and Gastric Adenocarcinoma Susceptibility in the Northwest Chinese Population

PLCE1 Polymorphisms and Risk of Esophageal and Gastric Cancer in a Northwestern Chinese Population

The Influence of PSCA Gene Variation on Its Expression and Gastric Adenocarcinoma Susceptibility in the Northwest