To analyze and explore the association between the 1607(1G/2G) single nucleotide polymorphism (SNP) in promoter of matrix metalloproteinase-1 (MMP-1) gene and susceptibility of head and neck cancer (HNC) by Meta-analysis.

Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pace, but to date no comprehensive overview and quantitative summary has been available.

Hepatocellular carcinoma (HCC) is among the commonest kind of malignant tumors, which accounts for more than 500,000 cases of newly diagnosed cancer annually. Many microarray studies for identifying differentially expressed genes (DEGs) in HCC have been conducted, but results have varied across different studies. Here, we performed a meta-analysis of publicly available microarray Gene Expression Omnibus datasets, which covers five independent studies, containing 753 HCC samples and 638 non-tumor liver samples. We identified 192 DEGs that were consistently up-regulated in HCC vs. normal liver tissue. For the 192 up-regulated genes, we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis. To our surprise, besides several cell growth-related pathways, spliceosome pathway was also up-regulated in HCC. For further exploring the relationship between spliceosome pathway and HCC, we investigated the expression data of spliceosome pathway genes in 15 independent studies in Nextbio database ( https://www.nextbio.com/b/nextbioCorp.nb ). It was found that many genes of spliceosome pathway such as HSPA1A, SNRPE, SF3B2, SF3B4 and TRA2A genes which we identified to be up-regulated in our meta-analysis were generally overexpressed in HCC. At last, using real-time PCR, we also found that BUD31, SF3B2, SF3B4, SNRPE, SPINK1, TPA2A and HSPA1A genes are significantly up-regulated in clinical HCC samples when compared to the corresponding non-tumorous liver tissues. Our study for the first time indicates that many genes of spliceosome pathway are up-regulated in HCC. This finding might put new insights for people's understanding about the relationship of spliceosome pathway and HCC.

To date, case-control studies on the association between a single-nucleotide polymorphism (SNP) in the plasminogen activator inhibitor-1 (PAI-1) gene and polycystic ovary syndrome (PCOS) have provided controversial results.

A quantity of case-control studies have been performed to address the association between three cyclooxygenase-2(COX-2) polymorphisms (-1195G/A, -765G/C and +8473T/C) and the risk of hepatocellular carcinoma (HCC). However, previous research results are inconsistent. We conducted this meta-analysis to clarify the correlation between these COX-2 polymorphisms and HCC risk.

The relationship between glutathione S-transferase M1 (GSTM1) genetic polymorphisms and lung cancer has been reported previously. However, the results are not consistent. Therefore, to clarify the association between GSTM1 polymorphisms and lung cancer, we performed a meta-analysis based on published studies. We used the Revman 5.0 software to perform literature retrieval, article selection, data collection, and statistical analysis. We utilized a random-effect model to pool the odds ratios (ORs) and 95% confidence intervals (CIs). A total of 38 eligible studies including 5737 lung cancer patients and 6843 cancer-free control subjects were analyzed. We found no association between GSTM1 genetic polymorphisms and lung cancer risk (OR = 1.15, 95%CI = 0.98-1.36, P = 0.08). Including only Chinese individuals, we found no association between GSTM1 genetic polymorphisms and lung cancer risk (OR = 1.13, 95%CI = 0.97-1.32, P = 0.13). In conclusion, we found that GSTM1 polymorphisms are not associated with lung cancer risk.

Numerous studies have evaluated the association between CYP1A1 gene polymorphisms and hepatocellular carcinoma (HCC) risk. However, the specific association is still controversial. The aim of our study was to clarify the effects of CYP1A1 gene polymorphisms (3801 T＞C and A2455G) on HCC risk by conducting a meta-analysis. We conducted searches of the literature published in PubMed and EMBASE databases up to April 2014. We estimated the pooled odds ratio with its 95% confidence interval to assess the association using a fixed or random-effects model. Publication bias was investigated by the Begg funnel plot. Meta-analysis was performed using the STATA package version 12.0. Meta-analysis results showed no significant association between the CYP1A1 3801 T＞C polymorphism and HCC risk. In a subgroup analysis by nationality, we found a significant association between 3801 T＞C polymorphism and HCC risk in Asians (TT vs TC: OR = 0.77, 95%CI = 0.60-0.99). As for A2455G, the meta-analysis indicated no significant association between the CYP1A1 A2455G polymorphism and HCC risk. In conclusion, the 3801 T＞C polymorphism in the CYP1A1 gene may be related to increased risk of HCC in Asians. Conclusive evidence on the effects of the variants in HCC should be addressed in further studies.

The results of previous case-control studies examining the relationship between the interleukin (IL)-6 gene -174G>C polymorphism and lung cancer are controversial. In this study, we evaluated the relationship between the IL-6 gene -174G>C polymorphism and lung cancer. We selected 5 case-control studies related to the IL-6 gene -174G>C polymorphism and lung cancer by searching the PubMed, EMBase, Chinese Biomedical Literature Database, and Wanfang database. We utilized the Q-test and I2 test to determine heterogeneity between each study. To merge the odds ratios (OR) and 95% confidence intervals (CI), we utilized the fixed effects model and random effect model for analyses. The present study included 2801 patients with lung cancer and 3234 cancer-free control subjects. The meta-analysis revealed no association between the IL-6 gene -174G>C polymorphism and lung cancer in either genotype or allele distribution [CC+GC vs GG: OR = 1.04, 95%CI (0.86-1.26), P = 0.70; GG+GC vs CC: OR = 0.93, 95%CI (0.82-1.05), P = 0. 23; CC vs GG: OR = 1.08, 95%CI (0.95-1.23), P = 0.23; C allele vs D allele: OR = 1.03, 95%CI (0.96-1.11), P = 0.44]. We concluded that the IL-6 gene -174G>C polymorphism was not associated with lung cancer.

Oral squamous cell carcinoma (OSCC) is a common cancer world-wide that is highly lethal due to its recurrence and metastasis. Methylation is a common epigenetic mechanism that leads to gene silencing in tumors and could be a useful biomarker in OSCC. The prevalence of P16, death-associated protein kinase (DAPK) and O6-methylguanine-DNA-methyltransferase (MGMT) promoter hypermethylation in OSCC has been evaluated for several years while the results remain controversial.

Nasopharyngeal carcinoma (NPC) is a malignant cancer arising from the epithelial surface of the nasopharynx that mostly appears in advanced stages of the disease, leading to a poor prognosis. To date, a number of mRNA profiling investigations on NPC have been reported in order to identify suitable biomarkers for early detection. However, the results may be specific to each study with distinct sample types. In this study, an integrative meta-analysis of NPC transcriptome data was performed to determine dysregulated pathways, potentially leading to identification of molecular markers. Ten independent NPC gene expression profiling microarray datasets, including 135 samples from NPC cell lines, primary cell lines, and tissues were assimilated into a meta-analysis and cross-validation to identify a cohort of genes that were significantly dysregulated in NPC. Bioinformatics analyses of these genes revealed the significant pathways and individual players involving in cellular metabolism, cell cycle regulation, DNA repair, as well as ErbB pathway. Altogether, we propose that dysregulation of these molecular pathways in NPC might play a role in the NPC pathogenesis, providing clues, which could eventually translate into diagnostic and therapeutic approaches.

The CD95 gene plays a key role in regulating cell growth and tumor genesis. To date, several publications have focused on the CD95 rs1800682A/G site polymorphism and various types of tumors in Asians; however, this association is still controversial and obscure. Therefore, a meta-analysis combined with all publications to clarify this association is necessary.

Emerging evidence indicates that O(6)-methylguanine-DNA methyltransferase (MGMT) is a candidate for tumor suppression in several types of human tumors including colorectal cancer (CRC). However, the correlation between MGMT hypermethylation and clinicopathological characteristics of CRC remains unclear. In this study, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of MGMT hypermethylation on the incidence of CRC and clinicopathological characteristics. A comprehensive literature search was done from Web of Science, the Cochrane Library Database, PubMed, EMBASE, CINAHL, and the Chinese Biomedical Database for related research publications written in English and Chinese. Methodological quality of the studies was also evaluated. Analyses of pooled data were performed with Review Manager 5.2. Odds ratio (OR) and hazard ratio (HR) were calculated and summarized, respectively. Final analysis from 28 eligible studies was performed. MGMT hypermethylation is found to be significantly higher in CRC than in normal colorectal mucosa, the pooled OR from 13 studies including 1085 CRC and 899 normal colorectal mucosa, OR = 6.04, 95 % confidence interval (CI) = 4.69-7.77, p < 0.00001. MGMT hypermethylation is also significantly higher in colorectal adenoma than in normal colorectal mucosa, but it is significantly less compared to that in CRC patients. Interestingly, MGMT hypermethylation is correlated with sex status and is significantly higher in female than in male. MGMT hypermethylation is also associated with high levels of microsatellite instability (MSI). The pooled HR for overall survival (OS) shows that MGMT hypermethylation is not associated with worse survival in CRC patients. The results of this meta-analysis suggest that MGMT hypermethylation is associated with an increased risk and high levels of MSI and may play an important role in CRC initiation. However, MGMT hypermethylation may play an important role in the early stage of CRC progression and development, as well as having limited value in prediction of prognosis in CRC patients. We also discussed that MGMT may serve as a potential drug target of CRC.

Telomerase reverse transcriptase (TERT) rs2735940 polymorphism was found to be associated with increased cancer risk. However, recent studies reported controversial results. The aim of our study was to detect its relationship with cancer risk.

The microsomal epoxide hydrolase 1 (EPHX1) Tyr113His and His139Arg polymorphisms have been reported to be associated with esophageal cancer (EC) risk, yet the results of these previous results have been inconsistent or controversial. The objective of this study was to explore whether the EPHX1 Tyr113His and His139Arg polymorphisms confer risk to EC. The relevant studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct, and Chinese Biomedical Literature Database until May 2013. The association between the EPHX1 Tyr113His and His139Arg polymorphisms and EC risk was pooled by odds ratios (ORs) together with their 95% confidence intervals (95%CIs). A total of eight case-control studies with 1163 EC patients and 1868 controls (seven studies for both Tyr113His and His139Arg polymorphisms, one study only for Tyr113His polymorphism) were eventually identified. We found no association between EPHX1 Tyr113His and His139Arg polymorphisms and EC risk in overall population (For Tyr113His: His vs. Tyr: OR = 1.05, 95%CI = 0.95-1.15, P = 0.379; His/His vs. Tyr/Tyr: OR = 1.04, 95%CI = 0.88-1.22, P = 0.208; His/Tyr vs. Tyr/Tyr: OR = 0.96, 95%CI = 0.80-1.15, P = 0.577; His/His vs. His/Tyr + Tyr/Tyr: OR = 1.10, 95%CI = 0.96-1.26, P = 0.164; His/His + His/Tyr vs. Tyr/Tyr: OR = 1.01, 95%CI = 0.90-1.12, P = 0.543. For His139Arg: Arg vs. His: OR = 1.04, 95%CI = 0.94-1.14, P = 0.465; Arg/Arg vs. His/His: OR = 1.06, 95%CI = 0.91-1.24, P = 0.470; Arg/His vs. His/His: OR = 1.03, 95%CI = 0.91-1.16, P = 0.673; Arg/Arg vs. Arg/His + His/His: OR = 1.04, 95%CI = 0.85-1.27, P = 0.708; Arg/Arg + Arg/His vs. His/His: OR = 1.02, 95%CI = 0.93-1.13, P = 0.617). In subgroup analysis based on ethnicity, significant association has been found in neither EPHX1 Tyr113His nor His139Arg polymorphism. The current meta-analysis suggests no evidence of association between the EPHX1 polymorphism and EC risk.

Lung cancer is the leading cause of cancer-related mortality worldwide. Detection of promoter hypermethylation of tumor suppressor genes in exfoliated cells from the lung provides an assessment of field cancerization that in turn predicts lung cancer. The identification of genetic determinants for this validated cancer biomarker should provide novel insights into mechanisms underlying epigenetic reprogramming during lung carcinogenesis.

Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are common primary liver cancers worldwide. However, the survival and prognosis of ICC are much poorer than those of HCC, indicating the different molecular characteristics and mechanisms between ICC and HCC. To identify differentially expressed (DE) genes between ICC and HCC or combined hepatocellular-cholangiocarcinoma (CHC), we performed integrated analysis of publicly available microarray Gene Expression Omnibus (GEO) datasets by MetaOmics. Three GEO datasets comprising 32 ICC biochips, 77 HCC biochips, and 34 CHC biochips were available for the data integration. We identified 7313 DE genes between ICC and HCC, including 3650 upregulated genes and 3663 downregulated genes. The S100 family members on chromosome 1q21 were extensively upregulated in ICC, and S100A11 had the greatest degree of upregulation in ICC. Based on the DE genes, combined gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed the enhanced pathways of local adhesion, ECM-receptor interaction, and regulation of action cytoskeleton, suggesting the enhanced communication between ICC and the microenvironment. Additionally, development-related genes and development-related pathways, including the Notch, Wnt, and TGF-β signaling pathways, were shown to be active prominently in ICC. Taken together, we identified the characteristically upregulated or downregulated DE genes and pathways in ICC compared with HCC or CHC. These DE genes and pathways supply new transcriptomics evidence for ICC and could help identify new therapeutic targets.

MicroRNA-21 (miRNA-21 or miR-21) may act as a prognostic biomarker of cancer. However, the available evidence is controversial. Therefore, the present meta-analysis summarizes this evidence and evaluates the prognostic role of this gene in breast cancer.

A novel fusion gene of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) has been recently identified in non-small-cell lung cancers (NSCLCs). Patients with the EML4-ALK fusion gene demonstrate unique clinicopathological and physiological characteristics. Here we present a meta-analysis of large-scale studies to evaluate the clinicopathological characteristics of NSCLC patients harboring the EML4-ALK fusion gene.

Glioblastoma multiforme (GBM) has a poor prognosis despite maximal multimodal therapy. Biomarkers of relevance to prognosis which may also identify treatment targets are needed. A few hundred genetic and molecular predictors have been implicated in the literature, however with the exception of IDH1 and O6-MGMT, there is uncertainty regarding their true prognostic relevance. This study analyses reported genetic and molecular predictors of prognosis in GBM. For each, its relationship with univariate overall survival in adults with GBM is described. A systematic search of MEDLINE (1998-July 2010) was performed. Eligible papers studied the effect of any genetic or molecular marker on univariate overall survival in adult patients with histologically diagnosed GBM. Primary outcomes were median survival difference in months and univariate hazard ratios. Analyses included converting 126 Kaplan-Meier curves and 27 raw data sets into primary outcomes. Seventy-four random effects meta-analyses were performed on 39 unique genetic or molecular factors. Objective criteria were designed to classify factors into the categories of clearly prognostic, weakly prognostic, non-prognostic and promising. Included were 304 publications and 174 studies involving 14,678 unique patients from 33 countries. We identified 422 reported genetic and molecular predictors, of which 52 had ⩾2 studies. IDH1 mutation and O6-MGMT were classified as clearly prognostic, validating the methodology. High Ki-67/MIB-1 and loss of heterozygosity of chromosome 10/10q were classified as weakly prognostic. Four factors were classified as non-prognostic and 13 factors were classified as promising and worthy of additional investigation. Funnel plot analysis did not identify any evidence of publication bias. This study demonstrates a novel literature and meta-analytical based approach to maximise the value that can be derived from the plethora of literature reports of molecular and genetic factors in GBM. Caution is advised in over-interpreting the results due to study limitations. Further research to develop this methodology and improvements in study reporting are suggested.

Mitochondrial microsatellite instability (mtMSI), a change in length in mtDNA microsatellite sequences between normal and tumor tissue, has been described as a frequent occurrence in colorectal cancer (CRC). We evaluated the prevalence and prognostic value of mtMSI and its relation to nuclear microsatellite instability (MSI) in patients with metastatic CRC (mCRC). At six loci (D310, D514, D16184, ND1, ND5, and COX1), the mitochondrial DNA sequence was analyzed in normal and tumor tissue, and the mtMSI status was determined. We evaluated the prevalence and outcome in terms of overall survival (OS) in 83 CRC patients with a MSI tumor (including 39 patients with Lynch syndrome) and in 99 mCRC patients with a microsatellite stable (MSS) tumor. A meta-analysis was performed to compare our findings with existing data. mtMSI at the D-loop region was found in 54.4 % (99 out of 182) of all patients. Prevalence of mtMSI was most pronounced at the D310 locus (50.5 %). Prevalence of mtMSI at the D-loop region was not different among patients with MSI compared to MSS tumors. There was no effect of mtMSI on prognosis in patients with MSI or MSS tumors. Prevalence of mtMSI was high in mCRC patients with both MSI and MSS tumors, but there was no correlation with prognosis. mtMSI was particularly present at the D310 locus.