Messenger RNA (mRNA) acts as template for protein synthesis. The matrix metalloproteinase-7 (MMP-7) protein and its mRNA expression have been suggested to be involved in the development of various diseases and cancers. We aimed to study associations between the MMP-7 protein and mRNA expression in gastric carcinoma (GC) patients. We searched in the Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, Current Contents Index, and several Chinese databases. Studies were pooled and odds ratios and their corresponding 95 % confidence intervals were calculated. Subgroup analyses and publication bias detection were also conducted. Statistical analysis was performed via Version 12.0 STATA software. An updated meta-analysis based on 16 independent cohort studies was performed to investigate this association. The study suggests that significant differences in MMP-7 protein levels were observed in tumor-node-metastasis (TNM) I-II vs. III-IV (odds radio (OR) =3.19, 95 % confidence interval (95%CI) =1.59 ∼ 6.41, P=0.001), in T1-2 vs. T3-4 invasive grade (OR=1.82, 95%CI=1.07 ∼ 3.12, P=0.028), and in distant metastasis-positive vs. metastasis-negative samples (OR=3.14, 95%CI=1.05 ∼ 9.35, P=0.040). Increased MMP-7 mRNA levels were found to be significantly correlated with invasive grade (T3-4 vs. T1-2: OR=5.61, 95%CI=2.64 ∼ 11.95, P<0.001) and in the lymph node (LN) metastasis (positive vs. negative: OR=7.08, 95%CI=4.20 ∼ 11.93, P<0.001) group. Country subgroup analysis yielded significantly different estimates in the protein expression of MMP-7 of all experimental groups. MMP-7 mRNA levels were increased in LN metastasis-positive GC in contrast to metastasis-negative in China and Korea (all P<0.05); this was not shown in Japan (P>0.05). Higher protein and mRNA levels of MMP-7 were statistically associated with aggressive LN metastasis, advanced TNM stage, and invasion in GC patients; MMP-7 can thus potentially serve as a useful biomarker in determining GC progression and prognosis.

Many existing studies have demonstrated that common polymorphisms in the hypoxia inducible factor-1α (HIF-1A) may contribute to the development of digestive tract cancers, but individually published studies showed inconclusive results. This meta-analysis aimed to derive a precise estimation of the relationships between HIF1A Pro582Ser polymorphism and the risk of digestive tract cancers. We searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM databases from inception through May 1, 2013. Meta-analysis was performed using the STATA 12.0 software. We assessed 6 case-control studies that included a total of 911 digestive tract cancer patients and 2774 healthy controls. Our meta-analysis indicated that HIF1A Pro582Ser polymorphism was associated with an increased risk of digestive tract cancer. Subgroup analysis by ethnicity suggested that HIF1A Pro582Ser polymorphism might increase an individual's susceptibility to digestive tract cancer in Asian populations. However, similar association was not observed in Caucasian populations. In conclusion, our findings suggest that HIF1A Pro582Ser polymorphism may contribute to the risk of digestive tract cancers, especially in Asian populations.

Several published articles have evaluated the association between the prostate stem cell antigen (PSCA) rs2294008 (C>T) polymorphism and bladder cancer risk, but the results remain inconclusive. In order to derive a more precise estimation of the association, we performed a meta-analysis of four case-control studies that included 9617 cases and 16,323 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Our meta-analysis showed that, overall, the rs2294008 (C>T) polymorphism was associated with bladder cancer susceptibility (OR = 1.29, 95%CI = 1.20-1.40 for TT vs CC; OR = 1.24, 95%CI = 1.16-1.31 for CT vs CC; OR = 1.25, 95%CI = 1.18-1.33 for TT/CT vs CC; OR = 1.13, 95%CI = 1.06-1.20 for TT vs CT/CC). In the stratified analyses, the risk remained significant for studies of European populations, Asian populations, population-based studies, and hospital-based studies. In conclusion, the results suggest that the PSCA rs2294008 (C>T) polymorphism is a risk factor for bladder cancer development.

The previous published data on the association between CYP1A2*F (rs762551), CYP1B1 Leu432Val (rs1056836), Asn453Ser (rs180040), and Arg48Gly (rs10012) polymorphisms and colorectal cancer risk remained controversial.

Acute lymphoblastic leukemia (ALL) arises due to several genetic alterations in progenitor cells, and methotrexate is frequently used as part of the treatment regimen. Although there is evidence for an effect of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) C677T and A1298C variations on drug response in ALL, its risk association for ALL is still unresolved. In a case-control study of 203 patients with ALL and 246 controls and meta-analysis in the Indian population, we showed an insignificant association of MTHFR C677T and A1298C genotypes with childhood and adult ALL. Comprehensive in silico characterization of non-synonymous single nucleotide polymorphisms (nsSNPs) and SNPs of the 3' untranslated region (UTR) revealed nine nsSNPs as deleterious, and three SNPs in the 3'UTR could possibly alter the binding of miRNAs. The study revealed that several overlooked SNPs may contribute to the risk of ALL susceptibility and further studies of these SNPs with functional characterization in a large sample size are required to understand the significant role of MTHFR in ALL development.

Inhibitor of DNA binding/differentiation protein 4 (ID4) is dominant negative helix loop helix transcriptional regulator is epigenetically silenced due to promoter hyper-methylation in many cancers including prostate. However, the underlying mechanism involved in epigenetic silencing of ID4 is not known. Here, we demonstrate that ID4 promoter methylation is initiated by EZH2 dependent tri-methylation of histone 3 at lysine 27 (H3K27me3). ID4 expressing (LNCaP) and non-expressing (DU145 and C81) prostate cancer cell lines were used to investigate EZH2, H3K27me3 and DNMT1 enrichment on ID4 promoter by Chromatin immuno-precipitation (ChIP). Enrichment of EZH2, H3K27Me3 and DNMT1 in DU145 and C81 cell lines compared to ID4 expressing LNCaP cell line. Knockdown of EZH2 in DU145 cell line led to re-expression of ID4 and decrease in enrichment of EZH2, H3K27Me3 and DNMT1 demonstrating that ID4 is regulated in an EZH2 dependent manner. ChIP data on prostate cancer tissue specimens and cell lines suggested EZH2 occupancy and H3K27Me3 marks on the ID4 promoter. Collectively, our data indicate a PRC2 dependent mechanism in ID4 promoter silencing in prostate cancer through recruitment of EZH2 and a corresponding increase in H3K27Me3. Increased EZH2 but decreased ID4 expression in prostate cancer strongly supports this model.

Growing evidence has indicated that lysyl oxidase (LOX) G473A polymorphism (rs1800449) is associated with cancer risk among Asians. However, results of single center and small sample study lack enough power. We first investigated the effect of LOX G473A polymorphism on cancer risk among Asians by a meta-analysis, and then further validated this association by a case-control study of colorectal cancer (CRC) with LOX G473A polymorphism in a Chinese population. STATA 12.0 software was used for the meta-analysis. The relationships were evaluated by calculating the pooled odds ratios (ORs) and their 95 % confidence intervals (CIs). In a case-control study comprising 577 CRC patients and 696 controls, LOX G473A polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Logistic regression was used to evaluate genetic associations with the occurrence of CRC. The results of our meta-analysis, including seven case-control studies with a total of 2,377 cancer patients and 2,499 controls, suggested that LOX G473A polymorphism might be associated with an increased risk of cancer among Asians. In addition, results of a case-control study indicated that individuals with the AA or AG genotype had a significantly increased susceptibility to CRC occurrence, compared with individuals who had GG genotype. Overall, this meta-analysis and case-control study of CRC observed convincing association of LOX G473A polymorphism with cancer risk in Asians; our study would contribute to complete elucidation of carcinogenesis.

Inflammation is a response of body tissues to injury or irritation. Small RNAs, such as miR-146a and miR-499, participate in various processes of tumorigenesis. A recent study indicates that inflammation and abnormal immune responses may promote malignant progression in cancer development, indicating that inflammation-related polymorphisms such as miR-146a rs2910164 and miR-499 rs3746444 are crucial. However, studies on the association of these two polymorphisms with hepatocellular carcinoma (HCC) are inconclusive and inconsistent. We aimed at accessing the combined result of reported studies and make a more precise estimate of the relationship.

Recent studies show that microRNA-145 (miR-145) might be an attractive tumor biomarker of considerable prognostic value. To clarify the preliminary predictive value of miR-145 for prognosis in various malignant neoplasms, we conducted a meta-analysis of 18 relevant studies.

The genetic basis of sporadic colorectal cancer (CRC) is not well explained by known risk polymorphisms. Here we perform a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, to identify genetic variants that contribute to CRC susceptibility. We replicate genome-wide statistically significant associations (P<5 × 10(-8)) in 16,823 cases and 18,211 controls of European ancestry. This study reveals a new pan-ethnic CRC risk locus at 10q25 (rs12241008, intronic to VTI1A; P=1.4 × 10(-9)), providing additional insight into the aetiology of CRC and highlighting the value of association mapping in diverse populations.

Various studies on association of glutathione S-transferase (GST) polymorphisms and childhood acute lymphoblastic leukemia (ALL) have yielded conflicting results. We examined this association among north Indian children and conducted an updated meta-analysis to overcome sample size-related limitations. GSTM1, GSTP1 and GSTT1 genotypes in 100 children with ALL and 300 healthy controls were compared. GSTT1 null mutation (odds ratio (OR) 2.54, 95% confidence interval (CI) 1.50-4.32) and GSTP1 homozygous mutation (OR 3.13, 95%CI 1.48-6.59) were found to increase the risk of childhood ALL, while GSTM1 did not alter the risk. Meta-analysis included 22, 10 and 20 studies examining the association of childhood ALL with GSTM1, GSTP1 and GSTT1 genotypes, respectively. Only GSTM1 genotype (OR 1.29, 95%CI 1.10-1.62) was associated with increased risk in the overall analysis. However, both GSTM1 (OR 1.54, 95%CI 1.12-2.10) and GSTT1 (OR 1.63, 95%CI 1.32-1.99) null genotypes were associated with increased risk in Asian subjects. The risk of developing childhood ALL was not associated with GSTP1 genotype.

We performed this meta-analysis to summarize all the results from available studies, aiming delineating the prognostic role of miRNA in esophageal cancer.

Hepatocellular Carcinoma (HCC) is one of the most common malignancy of liver and HCC-related morbidity and mortality remains at high level. Researchers had investigated whether and how reduced E-cadherin expression impacted the prognosis of patients with HCC but the results reported by different teams remain inconclusive.

The conclusions of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the risk of small-cell carcinoma of lung cancer are still debated. GSTP1 is one of the important mutant sites reported at present. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of small-cell carcinoma of lung cancer. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Ten reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and small-cell carcinoma of lung cancer. The G allele and GG genotype were not associated with the susceptibility of risk of small-cell carcinoma in overall populations, East-Asians and Turkish population. However, there was an association between GG genotype with the risk of small-cell carcinoma in Caucasians. In conclusion, GG genotype was associated with the risk of small-cell carcinoma in Caucasian patients with lung cancer. However, GSTP1 A/G gene polymorphism is not associated with the susceptibility of small-cell carcinoma in overall populations, East-Asians and Turkish population.

Previous case-control studies on the relation between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and lung cancer were controversial. In this study, we aimed to further evaluate the relation between the ACE gene I/D polymorphism and lung cancer.

The -1082A>G polymorphism is located in promoter region of interleukin-10 (IL-10) and it could affect the production of IL-10. Numerous studies have investigated the association between IL-10 -1082A>G and risk of digestive cancer. However, the conclusion is still inconsistent. Here, we have performed a meta-analysis and systematic review to determine the association between the IL-10 -1082A>G and susceptibility to digestive cancer. In this meta-analysis, we identified 40 eligible studies, involving 7195 patients of digestive cancer and 11755 controls. By pooling all eligible studies, we found the variant -1082G allele significantly increased risk of digestive cancer (G vs. A: OR = 1.181, 95% CI: 1.057-1.319). Further stratified analysis was performed to evaluate the influence of cancer types, ethnicities, study design, sample size and Hardy-Weinberg equilibrium. Stratified analysis suggested that, the -1082A>G polymorphism was only associated with increased risk for gastric cancer (G vs. A: OR = 1.281, 95% CI: 1.102-1.488) and in Asian population (G vs. A: OR = 1.399, 95% CI: 1.188-1.646). No significant publication bias was detected. Based on 40 studies and 18950 participants, we found the variant IL-10 -1082G allele significantly increased susceptibility to digestive cancer, especially for gastric cancer and in Asian population.

We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.

The X-ray repair cross-complementing group 1 (XRCC1) gene belongs to the family of DNA repair genes. Polymorphisms in the XRCC1 gene, Arg399Gln, Arg194Trp and Arg280His, have been reported to have implications in differentiated thyroid carcinoma (DTC) susceptibility, but the results remain conflicting and no meta-analysis has been published. Therefore, we carried out a systematic review of the published epidemiology studies, aiming to assess the relationship between XRCC1 polymorphisms and susceptibility to DTC risk. We selected three databases, PubMed, EMBASE and CNKI, in which to search for published literature. With respect to DTC risk associated with XRCC1, combined odds ratios (ORs) and 95% confidence intervals (CI) were appropriately calculated on the basis of co-dominant, dominant and recessive models. To investigate different effects from specific race, subgroup analyses were carried out in Asian and Caucasian populations. Eight studies meeting the inclusion criteria were eventually selected for Arg399Gln (1,550 cases and 2,692 controls), five studies for Arg194Trp (858 cases and 1,394 controls) and five studies for Arg280His (1,237 cases and 2,267 controls). The combined results of the relevant studies exhibited that no significant associations with DTC risk were demonstrated for polymorphisms in XRCC1 Arg399Gln, Arg194Trp and Arg280His in all genetic models. Stratified analyses in Asian and Caucasian populations showed similar results. This meta-analysis arrives at a conclusion that the XRCC1 (Arg399Gln, Arg194Trp, Arg280His) polymorphisms appear to confer no risk for DTC.

A number of single nucleotide polymorphisms have been associated with disease predisposition in chronic lymphocytic leukemia. A single nucleotide polymorphism in the MDM2 promotor region, MDM2SNP309, was shown to soothe the p53 pathway. In the current study, we aimed to clarify the effect of the MDM2SNP309 on chronic lymphocytic leukemia characteristics and outcome. We performed a meta-analysis of data from 2598 individual patients from 10 different cohorts. Patients' data and genetic analysis for MDM2SNP309 genotype, immunoglobulin heavy chain variable region mutation status and fluorescence in situ hybridization results were collected. There were no differences in overall survival based on the polymorphism (log rank test, stratified by study cohort; P=0.76; GG genotype: cohort-adjusted median overall survival of 151 months; TG: 153 months; TT: 149 months). In a multivariable Cox proportional hazards regression analysis, advanced age, male sex and unmutated immunoglobulin heavy chain variable region genes were associated with inferior survival, but not the MDM2 genotype. The MDM2SNP309 is unlikely to influence disease characteristics and prognosis in chronic lymphocytic leukemia. Studies investigating the impact of individual single nucleotide polymorphisms on prognosis are often controversial. This may be due to selection bias and small sample size. A meta-analysis based on individual patient data provides a reasonable strategy for prognostic factor analyses in the case of small individual studies. Individual patient data-based meta-analysis can, therefore, be a powerful tool to assess genetic risk factors in the absence of large studies.

Methylenetetrahydrofolate (MTHFR) is the key enzyme of the folate metabolic pathway and several studies have pointed to association between the MTHFR C677T polymorphism and breast cancer risk. Although significant association was observed in some studies, in others no clear link could be established.