Metastasis-associated protein 1 as a new prognostic marker for solid tumors: a meta-analysis of cohort studies

Metastasis-associated protein 1 (MTA1) is a molecular marker in various solid tumors that has recently been investigated. The prognostic significance of MAT1 expression remains controversial. In this work, we aimed to determine the relationship between immunohistochemistry-detected MAT1 expression and survival of patients with solid tumors by conducting a meta-analysis of cohort studies. Relevant studies were identified via an electronic database search updated on October 28, 2013. We included cohort studies that reported hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (CIs) to determine the association of high MTA1 expression with overall survival (OS) and clinicopathological characteristics. Heterogeneity was quantified using I ² statistics, and publication bias was evaluated using funnel plots. Sensitivity analysis was conducted to evaluate the robustness of meta-analysis findings. We identified 16 cohort studies that focused on MTA1 overexpression and prognosis involving 2,253 cancer patients. Overall, the combined HR for OS was 1.85 (95 % CI: 1.55–2.28, P?<?0.001). Omission of any single study had no significant effect on the pooled HR estimate. When the studies were stratified by tumor type, similar results of poor prognosis were observed in non-small cell lung cancer (HR?=?2.05, 95 % CI: 1.14–3.68, P?=?0.016) and esophageal squamous cell carcinoma (HR?=?1.86, 95 % CI: 1.44–2.39, P?<?0.001). Moreover, multivariate survival analysis showed that MTA1 overexpression was an independent predictor of poor prognosis (HR?=?1.90, 95 % CI: 1.53–2.37, P?<?0.001). In addtional, MTA1 overexpression was significantly associated with tumor size (OR?=?2.72, 95 % CI?=?1.44–5.14, P?=?0.002), tumor stage (OR?=?2.44, 95 % CI?=?1.67–3.57, P?<?0.001), depth of invasion (OR?=?2.63, 95 % CI?=?1.74–3.97, P?<?0.001), and lymph node metastasis (OR?=?2.57, 95 % CI?=?1.57–4.19, P?<?0.001). However, when age, sex, and tumor differentiation were considered, no obvious association was observed. This study provides a comprehensive examination of the literature available on the association of MTA1 overexpression with OS and some clinicopathological features in solid tumors. Meta-analysis results provide evidence that MTA1 may be a new indicator of poor cancer prognosis. Considering the limitations of the eligible studies, other large-scale prospective trials must be conducted to clarify the prognostic value of MTA1 in predicting cancer survival.     

TERT rs2736100 polymorphism contributes to lung cancer risk: a meta-analysis including 49,869 cases and 73,464 controls

Some studies investigated the association of TERT rs2736100 polymorphism with lung cancer (LC). But the results were not consistent. We performed a meta-analysis to examine the association between rs2736100 and LC. Databases including PubMed, EMBASE, Wanfang, and China National Knowledge Infrastructure (CNKI) were searched. Data were extracted, and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated. A total of 19 studies including 49,869 cases and 73,464 controls were involved in this meta-analysis. Overall, a significant association between TERT rs2736100 polymorphism and LC risk was observed (OR?=?1.23, 95 % CI 1.18–1.28, P?<?0.00001). This polymorphism was also significantly associated with LC risk in Asians (OR?=?1.27, 95 % CI 1.22–1.33, P?<?0.00001), Caucasians (OR?=?1.14, 95 % CI 1.10–1.18, P?<?0.00001), female patients (OR?=?1.37, 95 % CI 1.24–1.51, P?<?0.00001), male patients (OR?=?1.23, 95 % CI 1.15–1.31, P?<?0.00001), adenocarcinoma patients (OR?=?1.35, 95 % CI 1.28–1.41, P?<?0.00001), squamous cell carcinoma patients (OR?=?1.13, 95 % CI 1.04–1.21, P?=?0.002), small cell lung cancer patients (OR?=?1.09, 95 % CI 1.03–1.16, P?=?0.004), current smokers (OR?=?1.22, 95 % CI 1.17–1.27, P?<?0.00001), former smokers (OR?=?1.14, 95 % CI 1.08–1.21, P?<?0.0001), and never smokers (OR?=?1.37, 95 % CI 1.31–1.43, P?<?0.00001), respectively. This meta-analysis suggested that TERT rs2736100 polymorphism was a risk factor for LC.     

Pathological and prognostic significance of hypoxia-inducible factor 1α expression in epithelial ovarian cancer: a meta-analysis

Hypoxia-inducible factor-1α (HIF-1α) plays an important role in tumour progression and metastasis. However, the association between HIF-1α and clinicopathological characteristics of epithelial ovarian cancers is controversial. We searched articles on the association between HIF-1α expression and clinicopathological variables of epithelial ovarian cancer in Cochrane Library, Pubmed, Web of Knowledge and China National Knowledge Infrastructure (CNKI) from inception to February 2014. Twenty-five studies were included in the final review. The expression of HIF-1α in cancer or borderline tissue was significantly higher than that in benign tissue (cancer vs. benign, odds ratio (OR) = 9.73 (95 % confidence interval (CI), 4.90, 19.32); P?P?P?=?0.04). The expression of HIF-1α in stages III–IV or lymph node metastasis was significantly higher than that in stages I–II or that without lymph node metastasis, respectively (OR?=?3.01 (95 % CI, 1.92–4.74); P?P?=?0.0004). HIF-1α was associated with histological grade of cancer (grades 3 vs. 1, OR?=?4.52 (95 % CI, 2.79–7.31); P?P?=?0.003; grades 3 vs. 1, OR?=?2.43 (95 % CI), 1.65–3.59; P?P?P?=?0.94; OR?=?1.06 (95 % CI, 0.73–1.55); P?=?0.75). In conclusion, HIF-1α is related to the malignant degree, FIGO stage, histological grade, lymph node metastasis and 5-year survival rate of epithelial ovarian cancer. It may play an important role in clinical treatment and prognostic evaluation.     

Interleukin-6 −634C/G polymorphism is associated with lung cancer risk: a meta-analysis

Several studies have examined the associations of polymorphisms in interleukin-6 (IL6) with lung cancer (LC) risk. However, the results were conflicting. Thus, a meta-analysis was conducted to determine the relationship between IL6 polymorphisms and LC risk. Databases including PubMed, EMBASE, Wanfang, and China National Knowledge Infrastructure (CNKI) were searched. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Thirteen studies were included in this meta-analysis. Overall, a significant association between IL6 ?634C/G polymorphism and LC susceptibility was observed for GG?+?CG vs. CC (OR?=?1.33, 95 % CI 1.20–1.47, P?<?0.00001). This polymorphism was also significantly associated with LC risk in Asians (OR?=?1.33, 95 % CI 1.20–1.47, P?<?0.00001), female patients (OR?=?1.30, 95 % CI 1.11–1.52, P?=?0.0009), male patients (OR?=?1.25, 95 % CI 1.03–1.52, P?=?0.02), non-small cell lung cancer patients (OR?=?1.21, 95 % CI 1.03–1.41, P?=?0.02), small cell lung cancer patients (OR?=?1.91, 95 % CI 1.23–2.97, P?=?0.004), smokers (OR?=?1.42, 95 % CI 1.21–1.65, P?<?0.0001), and non-smokers (OR?=?1.32, 95 % CI 1.13–1.53, P?=?0.0003), respectively. No significant result was found for IL6 ?174C/G polymorphism. This meta-analysis suggested that IL6 ?634C/G polymorphism was a risk factor for LC.     

Prognosis and Clinicopathology of CXCR4 in Colorectal Cancer Patients: a Meta-analysis

The chemokine receptor 4 (CXCR4) has been widely used in diagnosis and prognosis of colorectal cancer(CRC). However, there is no current consensus on the impact of CXCR4 on CRC patients. The purpose of thisstudy was to evaluate the prognostic and clinicopathological importance of CXCR4 in CRC patients. Databases,such as PubMed, Cochrane library, CBM and EMBASE updated to 2014 were searched to include eligible articles.We analysed correlations between CXCR4 expression and clinicopathological features and overall survival(OS). A total of 1, 055 CRC patients from twelve studies were included in the study. The pooled odds ratios(ORs) which indicated CXCR4 expression was likely to be associated with TNM stage (OR=0.43, CI=0.34-0.55,P<0.00001), lymph node status (OR=2.23, CI=1.23-4.05, P=0.008) and vascular invasion (OR=2.21, CI=1.11-4.39,P=0.02). Poor overall survival of CRC cancer was found to be significantly related to CXCR4 overexpression(hazard ratio (HR) 1.36 CI=1.17-1.59, P<0.0001), whereas combined ORs revealed that CXCR4 expression hadno correlation with gender or differentiation. Based on the published studies, CXCR4 overexpression in patientsw ith CRC indicates poor survival outcome and clinicopathological factors.     

The expression of CXCL12 and CXCR4 in gastric cancer and their correlation to lymph node metastasis

The purpose of this study was to investigate the expression of CXCL12 and its receptor CXCR4 in gastric cancer and to determine their relationship with lymph node metastasis. Fifty patients with pathologically confirmed gastric cancer were analyzed from September 2004 to December 2004. The expression levels of CXCL12 and CXCR4 were examined by immunohistochemical staining in the primary gastric tumor tissues, adjacent normal mucosa tissues, and metastatic lymph nodes and were analyzed along with clinicopathological risk factors, to determine their correlation with the prognosis. Positive staining for CXCL12 and CXCR4 was identified in 90.0 and 80.0% of the primary gastric tumor tissues, respectively, with significantly higher expression intensities observed in the primary gastric tumor tissues than in the adjacent normal mucosa tissues (P?<?0.01 and P?=?0.01, respectively). Positive staining for CXCL12 and CXCR4 was identified in 94.4 and 91.7% of metastatic lymph nodes, respectively, with significantly higher expression intensities in the metastatic lymph nodes than in the adjacent normal mucosa tissues (P?<?0.01 and P?=?0.01, respectively). Expression of CXCL12 in the primary gastric tumor tissues was not significantly associated with the clinicopathological characteristics of the tumor or the disease prognosis. However, the intensity of CXCR4 staining in primary tumor tissues was positively related with lymph node metastasis, TNM staging, and disease prognosis (P?=?0.04, 0.03, 0.03, respectively). CXCL12 and CXCR4 are related to formation of gastric tumors and lymph node metastasis. Furthermore, the expression of CXCR4 could be used as a biomarker to predict malignant features of gastric cancer.     

Role of EZH2 protein expression in gastric carcinogenesis among Asians: a meta-analysis

The present meta-analysis aggregated the results of relevant studies to identify the role of zeste homolog 2 (EZH2) expression in gastric carcinogenesis among Asians. Related articles were found by searching the following electronic databases without language restrictions: PubMed, SpringerLink, Karger Medical and Scientific Publishers, Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Google Scholar. Meta-analysis was performed using STATA statistical software. Crude odds ratios (ORs) or hazard ratios (HRs) with their corresponding 95 % confidence interval (95 % CI) were calculated. Ten relevant studies, which enrolled a total of 872 gastric cancer patients, were selected for statistical analysis. The most important findings of our meta-analysis was that cancer tissues exhibited higher expression levels of EZH2 protein than normal, adjacent and benign tissues (cancer tissues vs normal tissues: OR?=?32.15, 95 % CI 22.58?~?45.79, P?<?0.001; cancer tissues vs adjacent tissues: OR?=?16.10, 95 % CI 11.35?~?22.84, P?<?0.001; cancer tissues vs benign tissues: OR?=?2.66, 95 % CI 1.89?~?3.75, P?<?0.001; respectively). Furthermore, we observed positive correlations between EZH2 expression and the TNM stage (OR?=?2.86, 95 % CI 1.72?~?4.75, P?<?0.001) as well as lymph node metastasis (OR?=?3.02, 95 % CI 2.01?~?4.53, P?<?0.001) of patients with gastric carcinoma. The correlation between EZH2 expression and gastric cancer prognosis was also evaluated in the meta-analysis. Statistical analysis demonstrated that the overall survival (OS) of EZH2-negative patients was shorter than that of patients with positive expressions of EZH2 (HR?=?0.54, 95 % CI?=?0.05?~?1.03, P?=?0.032). Our meta-analysis confirmed the view that EZH2 expression might participate in the development of gastric carcinogenesis. Thus, EZH2 protein may be a valuable biomarker for the diagnosis and prognosis of gastric cancer.     

Tumor necrosis factor-α 238 G/A polymorphism and gastric cancer risk: a meta-analysis

Though many studies were performed to assess the association between tumor necrosis factor-α (TNF-α) 238 G/A polymorphism and gastric cancer risk, there were no conclusive findings. A meta-analysis of previous published studies was performed to get a comprehensive assessment of the association between TNF-α 238 G/A polymorphisms and gastric cancer. The pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated to assess the association. Fifteen studies with a total of 7,795 participants were finally included into this meta-analysis. Overall, there was an obvious association between TNF-α 238 G/A polymorphism and increased risk of gastric cancer (A vs. G: OR?=?1.32, 95 % CI 1.02–1.72, P?=?0.036; GA vs. GG: OR?=?1.32, 95 % CI 1.01–1.72, P?=?0.042; and AA/GA vs. GG: OR?=?1.34, 95 % CI 1.02–1.76, P?=?0.036). Subgroup analysis by ethnicity showed the statistically significant association between TNF-α 238 G/A polymorphism and gastric cancer was limited to Asian populations (A vs. G: OR?=?1.59, 95 % CI 1.29–1.97, P?<?0.001; GA vs. GG: OR?=?1.63, 95 % CI 1.29–2.04, P?<?0.001; and AA/GA vs. GG: OR?=?1.64, 95 %CI 1.31–2.05, P?<?0.001), and there was no obvious association in Caucasians. In conclusion, TNF-α 238 G/A polymorphism is significantly associated with increased risk of gastric cancer, especially in Asians.     

Survival benefit of hepatic resection versus transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: a systematic review and meta-analysis

Background

No consensus treatment has been reached for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Hepatic resection (HR) and transarterial chemoembolization (TACE) have been recommended as effective options, but which is better remains unclear. This meta-analysis is to compare the effectiveness of HR and TACE for HCC with PVTT patients.

Methods

The PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched for comparing HR and TACE treating PVTT.

Results

Twelve retrospective studies with 3129 patients were included. A meta-analysis of 11 studies suggested that the 1-, 2-, 3-, and 5-year overall survival (OS) rates (OR?=?0.48, 95% CI?=?0.41–0.57, I² =?37%, P?<?0.00001; OR?=?0.21, 95% CI?=?0.12–0.38, I² =?43%, P?<?0.00001; OR?=?0.35, 95% CI?=?0.28–0.44, I² =?53%, P?<?0.00001; OR?=?0.28, 95% CI?=?0.14–0.54, I² =?72%, P?=?0.0001, respectively) favored HR over TACE. In a subgroup analysis, HR had better 1-, 2-,3, 5-year OS for type I PVTT (OR?=?0.33, 95% CI?=?0.17–0.64, I² =?20%, P?=?0.001; OR?=?0.32, 95% CI?=?0.16–0.63, I2?=?0%, P?=?0.001; OR?=?0.18, 95% CI?=?0.09–0.36, I2?=?0%, P?<?0.00001; OR?=?0.07, 95% CI?=?0.01–0.32, I2?=?0%, P?=?0.0006, respectively) and better 1-, 3-, and 5-year OS for type II PVTT (OR?=?0.37, 95% CI?=?0.20–0.70, I² =?59%, P?=?0.002; OR?=?0.22, 95% CI?=?0.13–0.39, I² =?0%, P?<?0.00001; OR?=?0.16; 95% CI?=?0.03–0.91; I² =?51%, P?=?0.04, respectively). There was no difference in 1-, 3-, or 5-year OS between HR and TACE for type III PVTT (OR?=?0.86, 95% CI?=?0.61–1.21, I² =?0%, P?=?0.39; OR?=?0.83, 95% CI?=?0.42–1.64, I² =?0%, P?=?0.59; OR?=?0.59, 95% CI?=?0.06–-6.04, I² =?65%, P?=?0.66, respectively).

Conclusions

HR may lead to longer OS for some selected HCC patients with PVTT than TACE, especially for type I or II PVTT, with less difference being observed for type III or IV PVTT.

     

Cleft lip and palate transmembrane protein 1 rs31489 polymorphism is associated with lung cancer risk: a meta-analysis

The potentially functional polymorphism, rs31489, in the promoter region of cleft lip and palate transmembrane protein 1 (CLPTM1L) gene has been implicated in cancer risk. However, individual published studies showed inconclusive results. To obtain a more precise estimate of the association between CLPTM1L rs31489 and risk of lung cancer, we performed a meta-analysis. Summary odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were estimated using random-effects models. Ten individual case–control studies in eight publications with 20,680 cases and 28,330 controls were included. Overall, the variant genotypes were associated with a significantly increased lung cancer risk in different genetic models (CC + AC vs. AA: OR?=?1.20, 95 % CI 1.12–1.28, P?<?0.001; CC vs. AC + AA: OR?=?1.15, 95 % CI 1.07–1.23, P?<?0.001; CC vs. AA: OR?=?1.28, 95 % CI 1.17–1.41, P?<?0.001; CC vs. AC: OR?=?1.11, 95 % CI 1.05–1.17, P?<?0.001; C vs. A: OR?=?1.12, 95 % CI 1.06–1.18, P?<?0.001). In the stratified analyses, the increased lung risk remained for the studies of Caucasian populations. In conclusion, this meta-analysis suggested that CLPTM1L rs31489 was a potential biomarker for lung cancer risk in Caucasians.     

Significant association between cytotoxic T lymphocyte antigen 4 +49G>A polymorphism and risk of malignant bone tumors

Cytotoxic T lymphocyte antigen 4 (CTLA-4) gene +49G>A polymorphism was implicated to be associated with risk of malignant bone tumors, but the finding was inconclusive owing to the limited sample of a single study. The objective of the current study was to conduct a pooled analysis of four previously published studies to investigate the association between CTLA-4 +49G>A polymorphism and the risk of malignant bone tumors. Data were extracted, and the pooled odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) was calculated to assess the association. Those four published studies included a total of 2,165 subjects. The pooled results indicated that CTLA-4 +49G>A polymorphism was significantly associated with risk of malignant bone tumors (AA versus GG: OR?=?2.24, 95 % CI 1.67–2.99, P?<?0.001; AA/GA versus GG: OR?=?1.35, 95 % CI 1.14–1.61, P?=?0.001; AA versus GG/GA: OR?=?2.00, 95 % CI 1.53–2.62, P?<?0.001). Stratified analyses by tumor type showed that CTLA-4 +49G>A polymorphism was associated with risks of both osteosarcoma (AA versus GG: OR?=?2.23, 95 % CI 1.45–3.43, P?<?0.001; AA/GA versus GG: OR?=?1.35, 95 % CI 1.04–1.75, P?=?0.024; AA versus GG/GA: OR?=?2.00, 95 % CI 1.34–2.98, P?=?0.001) and Ewing's sarcoma (AA versus GG: OR?=?2.24, 95 % CI 1.51–3.31, P?<?0.001; AA/GA versus GG: OR?=?1.36, 95 % CI 1.07–1.72, P?=?0.011; AA versus GG/GA: OR?=?2.01, 95 % CI 1.39–2.89, P?<?0.001). Therefore, results from the current pooled analysis suggest that CTLA-4 +49G>A polymorphism is associated with risk of malignant bone tumors, including osteosarcoma and Ewing's sarcoma.     

The prognosis and clinicopathology of CXCR4 in gastric cancer patients: a meta-analysis

The chemokine receptor 4 (CXCR4) has been widely investigated in diagnosis and prognosis of gastric cancer (GC). However, the impact of CXCR4 on GC patients remains controversial; Here, we conducted a meta-analysis to obtain the precise role of CXCR4 in GC prognosis and clinicopathology. Thirteen published studies with a total of 1,936 patients were included. Original data included the hazard ratio (HR) of overall survival (OS) and odds ratio (OR) in GC patients. We combined HR/OR with 95 % confidence interval (CI) to estimate the hazard. In this study, OS was significantly related to CXCR4 expression, with the HR 2.63 (95 % CI 1.69–4.09; p?<?0.0001), and a significant correlation was also revealed between CXCR4 expression and stage (I?+?II, +) (OR 0.52, 95 % CI 0.32–0.83; p?=?0.007), depth of invasion (T1/T2, +) (OR 0.44, 95 % CI 0.27–0.73; p?=?0.001), lymph node metastasis (LN, +) (OR 2.30, 95 % CI 1.57–3.36; p?<?0.0001), as well as vascular invasion (vas.inv, +) (OR 0.72, 95 % CI 0.53–0.98; p?=?0.04). Heterogeneity was observed among the included studies with OS (I ²?=?51 %), stage (I ²?=?78 %), depth of invasion (I ²?=?74 %), lymph node metastasis (I ²?=?64 %), and histology differentiation (I ²?=?79 %). No publication bias was observed. In conclusion, this meta-analysis showed CXCR4 expression indicates poor prognosis in GC patients with advanced stage or deep invasion in GC tissues, which also implied lymph node metastasis and vascular invasion. Thus, CXCR4 could help predict patient prognosis and guide clinical diagnosis and treatment.     

P53 codon 72 polymorphism and lung cancer risk: evidence from 27,958 subjects

The role of p53 codon 72 polymorphism in the development of lung cancer remains obscure due to inconsistent findings of individual case–control studies published to date. A meta-analysis was conducted to better estimate the association between the p53 codon 72 variant and lung cancer risk. All relevant publications from the PubMed, Embase, Web of Science, and Wanfang databases were retrieved. Based on the inclusion criteria, 39 publications involving 44 independent case–control studies were finally included into this meta-analysis. Data were extracted and the pooled odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) was calculated. The overall pooled ORs showed no significant relationship of the p53 codon 72 polymorphism with increased or decreased risk of lung cancer in all gene contrast models (OR _{Pro vs. Arg}?=?1.04, 95 % CI?=?0.96–1.13, P _OR?<?0.001; OR _{Pro/Pro vs. Arg/Arg}?=?1.07, 95 % CI?=?0.91–1.25, P _OR?<?0.001; OR _{Arg/Pro vs. Arg/Arg} =1.04, 95 % CI?=?0.94–1.15, P _OR?<?0.001; OR _{Pro/Pro + Arg/Pro vs. Arg/Arg}?=?1.04, 95 % CI?=?0.94–1.16, P _OR?<?0.001; OR _{Pro/Pro vs. Arg/Arg + Arg/Pro}?=?1.07, 95 % CI?=?0.93–1.23, P _OR?<?0.001). According to the ethnicity, no significant association was observed in subgroup analyses of the Asians, Caucasians, Africans and the mixed population. Similar finding was found in subgroup analyses of hospital-based and population-based studies. Concerning the histological types of lung cancer, the p53 codon 72 variant exerts risk effect on the lung carcinogenesis in patients with adenocarcinoma (OR _{Arg/Pro vs. Arg/Arg}?=?1.10, 95 % CI?=?1.00–1.22, P _OR?=?0.048). Additionally, subgroup analysis by the smoking status demonstrated that the p53 codon 72 variant seemed to play a protective role in lung carcinogenesis among the non-smokers but not the smokers in the contrast model of Arg/Pro vs. Arg/Arg (OR _{Arg/Pro vs. Arg/Arg}?=?0.71, 95 % CI?=?0.50–1.00, P _OR?=?0.049). The present meta-analysis suggests the p53 codon 72 polymorphism may weakly modify the risk for lung cancer among the adenocarcinoma patients and non-smokers. Nevertheless, this association needs further confirmation in future studies with high quality.     

PLCE1 rs2274223 A>G polymorphism and cancer risk: a meta-analysis

Phospholipase C epsilon 1 gene (PLCE1) encodes a phospholipase enzyme which regulates various physiological processes (cell growth, differentiation, and apoptosis) and is supposed to play a critical role in carcinogenesis. Recently, a single nucleotide polymorphism (rs2274223 A>G) in PLCE1 was reported as a novel susceptibility locus for esophageal and gastric cancers by genome-wide association studies performed in Chinese population. However, individual association studies replicating this finding showed inconclusive results. Therefore, we performed a meta-analysis of eligible studies to derive precise estimation of the association of PLCE1 rs2274223 A>G polymorphism with cancer risk. We performed pooled analysis of 12 case–control studies including 7,622 cases and 9,555 controls. Odds ratios and 95 % confidence interval were calculated to assess strength of association in overall studies and in subgroup analysis stratified by ethnicity, cancer types, and source of controls. All statistical analyses were performed by MIX 2.0 software. We found that PLCE1 rs2274223 A>G polymorphism was significantly associated with increased risk of cancer in log additive/dominant model and at allele level (GG vs. AA: OR?=?1.24, 95 % CI?=?1.01–1.53, P?=?0.039; AG vs. AA: OR?=?1.24, 95 % CI?=?1.16–1.32, P?<?0.001; AG?+?GG vs. AA: OR?=?1.22, 95 % CI?=?1.12–1.34, P?<?0.001; and G vs. A allele: OR?=?1.15, 95 % CI?=?1.05–1.25, P?=?0.002). Further, stratified analysis showed elevated risk of only gastric and esophageal tumors. Sub-group analysis based on ethnicity suggests PLCE1 polymorphism conferred significant risk among Asian (Chinese) but not in Caucasian. In conclusion, PLCE1 rs2274223 polymorphism may be used as potential biomarker for cancer susceptibility particularly for esophageal/gastric cancer and for the Chinese population.     

Lack of association between MTHFD1 G401A polymorphism and ovarian cancer susceptibility

Published studies on the association between methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) G401A polymorphism and ovarian cancer risk have yielded conflicting results. In order to derive a more precise estimation of the relationship between G401A polymorphism and ovarian cancer risk, the present meta-analysis was performed. All eligible studies on G401A polymorphism and ovarian cancer risk were collected from the PubMed and the Cochrane Library. Statistical analyses were performed by Review Manage 5.0 and Stata 11.0. Our analysis suggested that G401A polymorphism was not associated with ovarian cancer risk when using additive (odds ratio (OR)?=?1.72, 95 % confidence interval (CI)?=?1.34–2.20, P?<?0.0001), recessive (OR?=?1.46, 95 % CI?=?1.21–1.77, P?<?0.0001), dominant (OR?=?1.36, 95 % CI?=?1.10–1.69, P?=?0.004), and allelic models (OR?=?1.30, 95 % CI?=?1.15–1.47, P?<?0.0001) to analyze the data. This meta-analysis suggests that G401A polymorphism might not be a risk factor for ovarian cancer risk. However, further well-designed studies are required to confirm our findings.     

The CCND1 G870A polymorphism and susceptibility to bladder cancer

Published studies on the association between cyclin D1 (CCND1) G870A polymorphism and bladder cancer risk have yielded conflicting results. Thus, a systemic review and meta-analysis of published studies were performed to assess the possible association. All eligible studies of G870A polymorphism and bladder cancer risk were collected from the PubMed and the Cochrane Library. Statistical analyses were performed by Review Manager 5.0 and Stata 11.0. Significant association between G870A polymorphism and bladder cancer susceptibility was found under recessive model in overall population (OR?=?1.21, 95 % CI 1.01–1.45, P?=?0.04). When stratifying for the race, our analysis suggested that CCND1 G870A was associated with bladder cancer risk in Asians when using homogeneous codominant (OR?=?1.72, 95 % CI 1.34–2.20, P?<?0.0001), recessive (OR?=?1.46, 95 % CI 1.21–1.77, P?<?0.0001), dominant (OR?=?1.36, 95 % CI 1.10–1.69, P?=?0.004), and allelic models (OR?=?1.30, 95 % CI 1.15–1.47, P?<?0.0001) to analyze the data. However, no significant associations were found in Caucasians. After stratifying the studies by control source, G870A polymorphism was significantly associated with bladder cancer risk under recessive model (OR?=?1.31, 95 % CI 1.03–1.67, P?=?0.03) in hospital-based case–control studies, but not in population-based case–control studies. This meta-analysis suggested that G870A polymorphism most likely contributes to increased susceptibility to bladder cancer in the overall population, hospital-based case–control studies, and Asians.     

Prognostic and clinicopathological value of NM23 expression in patients with breast cancer: A systematic review and meta-analysis

It is hypothesized that, NM23, as a metastasis suppressor gene, may be a good indicator of patients with breast cancer in most reports. The aim of our meta-analysis was to determine the prognostic value of NM23 in patients with breast cancer synthetically, by searching 3 databases, PubMed, EMBASE, and Web of Science, for relevant articles. The inclusion criteria, exclusion criteria, and the standard-of-quality assessment were used according to a previous protocol. The pooled odd ratios (ORs) and corresponding 95% CI were calculated to assess the primary end point, survival data, and the secondary end point, associations between NM23 expression and clinicopathological factors. Finally, funnel plots and Egger׳s linear regression test were used to assess the potential publication bias. Overall, 792 articles were retrieved in the initial search of databases, and 4968 patients were eventually pooled from 26 available studies selected out by 2 independent reviewers. The incorporative OR showed that elevated NM23 expression was associated with better overall survival (OR = 0.62; 95% CI: 0.52-0.74; P < 0.00001; I² = 0%; Ph = 0.46). In disease-free survival, we also obtained a good prognosis (OR = 0.30; 95% CI: 0.18-0.48; P < 0.00001; I² = 46%; Ph = 0.13). In addition, high-NM23 expression was correlated with well or moderate histologic grade, negative lymph node metastasis, and early tumor staging. Furthermore, publication bias was detected in overall survival but not in disease-free survival, and it could also be verified by Egger׳s test (P = 0.009 and P = 0.687, respectively). These results implied that NM23 might be an indicator of good prognosis in patients with breast cancer, although further researches need to be performed to confirm the prognostic value of NM23.     

Meta-analysis: glutathione S-transferase T1 null allele is associated with gastric cancer risk

Allelic variant within genes encoding glutathione S-transferase T1 (GSTT1) has been suggested to be a possible risk factor of gastric cancer, but previous studies provide controversial results. This study aimed to assess the effects of GSTT1 polymorphism on gastric cancer by means of meta-analysis. We included published studies on the relationship between GSTT1 null allele and gastric cancer risk after searching electronic databases. A meta-analysis was conducted by calculating the pooled odds ratios (OR) and the 95 % confidence intervals (95 % CI). Forty-two studies with a total of 8,203 gastric cancer cases and 13,866 controls were included into this meta-analysis. When all 42 studies were pooled into this meta-analysis, there was a significant association between the GSTT1 null allele and gastric cancer risk (OR?=?1.24, 95 % CI 1.14–1.36, P?<?0.00001). Sensitivity analysis by excluding individual studies showed that there was no effect on the pooled OR with 95 % CI. After excluding studies with low quality, there was still a significant association between the GSTT1 null allele and gastric cancer risk (OR?=?1.24, 95 % CI 1.13–1.36, P?<?0.00001). In the subgroup analysis, there was a significant association between the GSTT1 null allele and gastric cancer risk in both Europeans and Asians. There was no risk of publication bias in this meta-analysis. Our results suggest that GSTT1 null allele is associated with increased risk of gastric cancer.     

Association between tumor necrosis factor-α rs1800629 polymorphism and risk of gastric cancer: a meta-analysis

Gastric cancer is mainly initiated by inflammation and chronic superficial gastritis, and tumor necrosis factor-α (TNF-α) is an inflammatory cytokine which plays an important role in the inflammation. TNF-α rs1800629 G/A polymorphism was proposed to be associated with gastric cancer risk, but previous studies on Caucasians reported conflicting results. We performed a meta-analysis to comprehensively assess the association between TNF-α rs1800629 polymorphism and gastric cancer risk in Caucasians. The pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to assess the association. Eleven case–control studies with 7,427 subjects were finally included into the meta-analysis. Overall, TNF-α rs1800629 polymorphism was significantly associated with the increased risk of gastric cancer under four genetic comparison models (A versus G: OR?=?1.32, 95 % CI 1.12–1.56, P?=?0.001; AA versus GG: OR?=?1.76, 95 % CI 1.37–2.26, P?<?0.001; AA versus GG/GA: OR?=?1.62, 95 % CI 1.27–2.07, P?<?0.001; AA/GA versus GG: OR?=?1.35, 95 % CI 1.14–1.60, P?=?0.001). Meta-analysis of those studies with high quality showed that TNF-α rs1800629 polymorphism was still significantly associated with the increased risk of gastric cancer under four genetic comparison models. There was no risk of publication bias in the meta-analysis. The meta-analysis suggests that TNF-α rs1800629 polymorphism is associated with the increased risk of gastric cancer in Caucasians.