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Background: Polymorphisms of genes encoding PSCA, PLCE1 and MUC1 have been associated with the risk of different cancers in genome wide association studies (GWAS). Up to date there are limited data on the role of these genetic alterations in colorectal cancer (CRC) development. The aim of this study was to evaluate potential associations between single nucleotide polymorphisms (SNPs) of genes encoding PSCA, PLCE1 and MUC1 and the presence of CRC in European populations., Materials and Methods: Gene polymorphisms were analyzed in 574 European subjects (controls: n=382; CRC: n=192). PSCA C>T (rs2294008), PSCA G>A (rs2976392), MUC1 A>G (rs4072037) and PLCE1 A>G (rs2274223) SNPs were genotyped by RT-PCR., Results: The distribution of genotypes for all four SNPs was in line with the Hardy-Weinberg equilibrium (rs2294008, P=0.153; rs2976392, P=0.269; rs4072037, P=0.609; rs2274223, P=0.858). The distribution of genotypes and alleles of PSCA C>T, PSCA G>A, MUC1 A>G and PLCE1 A>G SNPs was similar among controls and CRC patient groups (P>0.05). GG genotype of MUC1 SNP was more frequent in CRC patients (24.0%) than in controls (20.2%); however, this association failed to reach significance (OR-1.45, P=0.15). Overall, in the present study SNPs of PSCA (rs2294008, rs2976392), MUC1 (rs4072037) and PLCE1 (rs2274223) genes were not associated with the presence of CRC., Conclusions: Gene polymorphisms of PSCA, PLCE1 and MUC1 genes are not associated with the presence of CRC in European subjects.

Objective: To study the PLCE1 gene rs2274223 polymorphism with regard to esophageal cancer and its interaction with diet, lifestyle, psychological and environmental factors in Southwest Shandong province., Materials and Methods: A case series study (case-case) was conducted. Questionnaire data were collected and 3 ml-5 ml venous blood was drawn for DNA extraction among the qualified research subjects. PLCE1 gene polymorphism was detected after PCR amplification of DNA. SPSS 13.0 software was used for statistical analysis of the data., Results: The three genotypes A/A, A/G and G/G PLCE1 gene rs2274223 was 31, 16 and 4 cases, accounting for 60.8%, 31.4%, 0.08% respectively. The difference of three genotypes (AA/GA/GG) proportion between negative and positive family history of patients was statistically significant, χ2=6.213, p=0.045. There was no statistically significant relationship between PLCE1 gene rs2274223 polymorphism and smoking, drinking, χ2=0.119, p=0.998, and χ2=1.727, p=0.786. There was no linkage of the three rs2274223 PLCE1 gene genotypes (AA/GA/GG) proportion with eating fried, pickled, hot, mildew, overnight, smoked, excitant food, eat speed, salt taste or not (p>0.05). or with living environment pollution and nine risk factors of occupational exposure (p>0.05). There was no statistically significant difference in TS scores between different genotype of rs2274223 PLCE1 gene., Conclusions: The PLCE1 rs2274223 polymorphism has a relationship with family history of esophageal cancer, but does not have any significant association with age, gender, smoking, alcohol drinking, food hygiene, eating habits, living around the environment and occupation in cases.

Background: A number of studies have identified a shared susceptibility locus in phospholipase C epsilon 1 (PLCE1) for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA). However, the results of PLCE1 expression in esophageal and gastric cancer remain inconsistent and controversial. Moreover, the effects on clinicopathological features remain undetermined. This study aimed to provide a precise quantification of the association between PLCE1 expression and the risk of ESCC and GCA through meta-analysis., Materials and Methods: Eligible studies were identified from PubMed, Wanfang Data, ISI Web of Science, and the Chinese National Knowledge Infrastructure databases. Using RevMan5.2 software, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were employed to assess the association of PLCE1 expression with clinicopathological features relative to ESCC or GCA., Results: Seven articles were identified, including 761 esophageal and gastric cancer cases and 457 controls. Overall, we determined that PLCE1 expression was associated with tumor progression in both esophageal cancers (pooled OR=5.93; 95%CI=3.86 to 9.11) and gastric cancers (pooled OR=9.73; 95%CI=6.46 to 14.7). Moreover, invasion depth (pooled OR=3.62; 95%CI=2.30 to 5.70) and lymph node metastasis (pooled OR=4.21; 95%CI=2.69 to 6.59) were linked with PLCE1 expression in gastric cancer. However, no significant associations were determined between PLCE1 overexpression and the histologic grade, invasion depth, and lymph node metastasis in esophageal cancer., Conclusions: Our meta- analysis results indicated that upregulated PLCE1 is significantly associated with an increased risk of tumor progression in ESCC and GCA. Therefore, PLCE1 expression can be appropriately regarded as a promising biomarker for ESCC and GCA patients.

Background: Phospholipase C epsilon 1 (PLCE1) encodes a member of the phospholipase family of proteins that play crucial roles in carcinogenesis and progression of several cancers including esophageal cancer (EC). In two large scale genome-wide association studies (GWAS) single nucleotide polymorphisms (SNP, rs2274223A>G, rs3765524C>T) in PLCE1 were identified as novel susceptibility loci of esophageal cancer (EC) in China. The aim of the present study was to investigate this finding in Kashmir Valley, a high risk area., Materials and Methods: We determined genotypes of three potentially functional SNPs (rs2274223A>G, rs3765524C>T and rs7922612C>T) of PLCE1 in 135 EC patients, and 195 age and gender matched controls in Kashmiri valley by PCR RFLP method. Risk for developing EC was estimated by binary logistic regression using SPSS., Results: The selected PLCE1 polymorphisms did not show independent association with EC. However, the G2274223T3765524T7922612 haplotype was significantly associated with increased risk of EC (OR=2.92; 95% CI=1.30-6.54; p=0.009). Smoking and salted tea proved to be independent risk factors for EC., Conclusions: Genetic variations in PLCE1 modulate risk of EC in the high risk Kashmiri population.

Purpose: To investigate and study the relationship between the PLCE1 rs2274223 gene polymorphism and susceptibility to esophageal cancer by meta-analysis., Materials and Methods: The literature was searched in Wanfang, CNKI, PubMed, CBM, Web of Science, MEDLINE, EMBASE, Springer, Elsevier and Cochrane databases from the date of January 1st 2004 to April 1st 2014 to collect case-control studies on the PLCE1 polymorphism and susceptibility to esophageal cancer. For the population genotype distributions of both esophagus cancer and control groups, their odds ratios (ORs) and 95% confidence intervals (CIs) were taken as effect indexes. Disqualified studies were excluded. Odds ratios of PLCE1 rs2274223 genotype distributions in the group of patients with esophageal cancer and the group of healthy control were calculated. The meta- analysis software, RevMan5.0, was applied for heterogeneity test, pooled OR and 95% confidence intervals. Sensitivity analysis and publication bias were also explored., Results: A total of twelve case-control studies were included, covering a total of 9, 912 esophageal cancer cases and 13, 023 controls were included. The pooled odds ratio of PLCE1 rs2274223 genotype GA vs AA was 1.29 (95%CI=1.17~1.43), p<0.01, GG vs AA was 1.65 (95%CI=1.32~2.05), p<0.01, GG/GA vs AA was 1.30 (95%CI=1.16~1.46), p<0.01 and GG vs GA/AA was 1.48 (95%CI=1.22~1.80), p<0.01. The PLCE1 rs2274223 polymorphism was thus associated with risk of esophageal cancer in all genetic models. In the stratified analysis by ethnicity, and source of controls, no significantly increased risk was observed for white persons. There was no obvious publication bias detected., Conclusions: This meta-analysis showed there was a significantly association between PLCE1 rs2274223 polymorphism and esophageal cancer in yellow race populations. Due to some minor limitations, our findings should be confirmed in further studies.

Esophageal squamous cell carcinoma (ESCC) is one of the most malignancies with a poor prognosis. The phospholipase C? gene (PLCE1) encodes a novel ras-related protein effector mediating the effects of R-Ras on the actin cytoskeleton and membrane protrusion. However, molecular mechanisms pertinent to ESCC are unclear. We therefore designed PLCE1-special small interfering RNA and transfected to esophageal squamous cell (EC) 9706 cells to investigate the effects of PLCE1 gene silencing on the cell cycle and apoptosis of ESCC and indicate its important role in the development of ESCC. Esophageal cancer tissue specimens and normal esophageal mucosa were obtained and assayed by immunohistochemical staining to confirm overexpression of PLCE1 in neoplasias. Fluorescence microscopy was used to examine transfection efficiency, while the result of PLCE1 silencing was examined by reverse transcription (RT-PCR). Flow cytometry and annexin V apoptosis assays were used to assess the cell cycle and apoptosis, respectively. Expression of cyclin D1 and caspase-3 was detected by Western-blotting. The level of PLCE1 protein in esophageal cancer tissue was significantly higher than that in normal tissue. After transfection, the expression of PLCE1 mRNA in EC 9706 was significantly reduced, compared with the control group. Furthermore, flow cytometry results suggested that the PLCE1 gene silencing arrested the cell cycle in the G0/G1 phase; apoptosis was significantly higher than in the negative control group and mock group. PLCE1 gene silencing by RNAi resulted in decreased expression of cyclin D1 and increased expression of caspase-3. Our study suggests that PLCE1 may be an oncogene and play an important role in esophageal carcinogenesis through regulating proteins which control cell cycling and apoptosis.