Association between Cyclin D1 (CCND1) polymorphism and cervical cancer risk are conflicting with published articles. We performed a meta-analysis to investigate the association between CCND1 G870A polymorphism and cervical cancer risk.

Many genetic variations in the promoter region of tumor necrosis factor alpha (TNF-α) may confer host susceptibility to cancer by influencing TNF-α expression. Nevertheless, the results remain inconclusive. The current meta-analysis was performed to investigate the association between three common TNF-α promoter polymorphisms and the risk of non-Hodgkin lymphoma (NHL). A literature search was conducted mainly from PubMed for all eligible studies. The pooled odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were used to assess the association of TNF-α polymorphisms with the risk of NHL. TNF-α -308 A allele showed a statistically significant increased risk for NHL under the homozygous (AA vs. GG, OR = 1.51, 95 % CI = 1.26-1.80) and recessive (OR = 1.47, 95 % CI = 1.23-1.75) models, respectively. The stratified analyses showed an increased risk of NHL with the presence of TNF-α -308 A allele among Africans and Caucasians, but a decreased risk among Asians. No association was observed between -238 G/A polymorphism and NHL risk either in the overall analysis or in the stratified analysis. Similarly, pooled analysis did not reveal an altered risk of NHL with -857 C/T polymorphism. Nonetheless, a statistically significant association was observed among Asians when stratified by ethnicity. Among the three genetic variations of interest, TNF-α -308 G/A polymorphism was significantly associated with the risk of NHL; neither -238 G/A nor -857 C/T polymorphism was shown to alter the overall NHL risk; however, stratified analysis by ethnicity observed a statistically significant association between -857 C/T polymorphism and the risk of NHL among Asians.

MicroRNAs (miRNAs) have been proposed as promising diagnostic biomarkers for many diseases, particularly in the field of cancer research. Numerous studies have explored the use of miRNAs in the detection of hepatocellular carcinoma (HCC), with some reporting inconsistent results. Thus, we conducted this meta-analysis to evaluate the potential diagnostic value of miRNAs in HCC. All relevant literature was collected from the PubMed and other databases before June 3, 2014. The summary receiver operator characteristic (SROC) curve and other parameters were used to estimate overall predictive performance. Fourteen studies involving 1,848 cases with HCC and 1,187 controls (576 healthy controls and 611 individuals with chronic liver diseases) were included in this meta-analysis. SROC analyses for the diagnostic power of miRNAs yielded an area under the curve (AUC) of 0.93 with 86 % sensitivity and 86 % specificity in discriminating patients with HCC from healthy subjects and an AUC of 0.88 with 79 % sensitivity and 83 % specificity in differentiating patients with HCC from those with chronic liver diseases (CLDs). Furthermore, subgroup analyses showed that miRNA panels yielded excellent diagnostic characteristics, with an AUC of 0.99 (96 % sensitivity and 96 % specificity) for detection of HCC from healthy controls and an AUC of 0.93 (85 % sensitivity and 88 % specificity) for HCC from those with CLDs. MiRNAs might be novel potential biomarkers for the diagnosis of HCC, and a combination of multiple miRNAs could significantly improve the diagnostic accuracy.

To explore whether the functional chemokine receptor 5 delta32 (CCR5-Δ32) polymorphism is associated with susceptibility to cancer.

Various studies have assessed the diagnostic accuracy of EGFR mutation-specific antibodies in non-small cell lung cancer (NSCLC). We performed a meta-analysis of existing data to investigate the diagnostic value of mutation-specific antibodies for detection of EGFR mutations in NSCLC.

Epidermal growth factor receptor (EGFR) mutation is a reliable and sensitive biomarker for EGFR-TKI therapy in non-small-cell lung cancer (NSCLC). However, detection of EGFR mutation in tissues has obvious limitations. Circulating free DNA (cfDNA) has been reported as an alternative approach for the detection of EGFR mutations. This systematic review and meta-analysis was designed to assess the diagnostic performance of cfDNA, compared with tissues. True-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) values were extracted or calculated for each study. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall diagnostic performance. 20 eligible studies involving 2012 cases were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.674 (95%CI: 0.517-0.800), 0.935 (95%CI: 0.888-0.963), 10.307 (95%CI: 6.167-17.227), 0.348 (95%CI: 0.226-0.537), and 29.582 (95%CI: 4.582-60.012), respectively. The AUC was 0.93 (95% CI: 0.90-0.95). The meta-analysis suggests that detection of EGFR mutation by cfDNA is of adequate diagnostic accuracy and cfDNA analysis could be a promising screening test for NSCLC.

Emerging published data on the association between single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) gene and cancer susceptibility are inconsistent. This review and meta-analysis is performed to derive a more precise evaluation of this relationship.

A large body of genetic research has focused on the potential role that mitochondrial DNA (mtDNA) variants might play on the predisposition to common and complex (multi-factorial) diseases. It has been argued however that many of these studies could be inconclusive due to artifacts related to genotyping errors or inadequate design.

MT1-MMP exhibits diverse expressions in patients with cancer and could be considered as potential prognostic biomarker of cancer. We performed a meta-analysis aiming to provide more sufficient evidence that MT1-MMP expression is associated with poor overall survival in several types of cancers. We systematically searched the studies from databases and carefully identified based on eligibility criteria. The association between MT1-MMP expression and overall survival in cancers was estimated using Review Manager. A total of 11 literatures which included 1,918 cancer patients were combined in the final analysis. Meta-analysis revealed that MT1-MMP overexpression was associated with an unfavorable overall survival and the pooled hazard ratio (HR) and corresponding 95 % confidence interval (CI) was 2.46 (95 % CI 1.75-3.47). From subgroup analyses, we identified that MT1-MMP was an independent prognostic factor for lung cancer and gastric cancer, and HRs (95 % CI) were 3.73 (95 % CI 2.67-5.21) and 2.46 (95 % CI 1.69-3.59), respectively. In conclusion, MT1-MMP is a potential prognostic factor in human cancers.

Circulating microRNAs (miRNAs) have been reported to be aberrantly expressed in patients with breast cancer (BC) and thus may serve as potential diagnostic biomarkers. This meta-analysis aimed to assess the potential diagnostic value of using circulating miRNAs for BC. The summary receiver operator characteristic (SROC) curve was used to assess the overall diagnostic performance of circulating miRNA. All analyses were performed using STATA 12.0 software. Thirty-one studies from 16 publications with a total of 1,668 BC patients and 1,111 healthy controls were included in this meta-analysis. Our results showed that the pooled sensitivity (SEN) for miRNAs assays was 0.77 (95 % CI 0.69-0.84), specificity (SPE) was 0.88 (95 % CI 0.79-0.93), positive likelihood ratio (PLR) was 4.2 (95 % CI 3.0-6.0), negative LR (NLR) was 0.29 (95 % CI 0.21-0.40), and diagnostic odds ratio (DOR) was 18 (95 % CI 10-32). The area under the SROC curve (AUC) was 0.89 (95 % CI 0.86-0.91). Subgroup analysis suggested that employing a combination of multiple miRNAs was better than using a single miRNA in SEN (0.88 vs. 0.69), SPE (0.88 vs. 0.89), PLR (6.3 vs. 3.3), NLR (0.14 vs. 0.41), DOR (48 vs. 10), and AUC (0.94 vs. 0.83). In conclusion, our meta-analysis suggested that the expression profiles of circulating miRNAs, especially using a combination of them, have potential to facilitate accurate breast tumor detection. However, there are still challenges that need to be addressed to establish these new biomarkers before they can be applied to routine clinical procedures.

The association between CCAAT/enhancer binding protein-ε (CEBPE) rs2239633 polymorphism and acute lymphoblastic leukemia (ALL) risk has been reported, but results of previous studies remain controversial and ambiguous. To assess the association between CEBPE rs2239633 polymorphism and childhood ALL risk, a meta-analysis was performed. Based on comprehensive searches of the PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM), we identified outcome data from all articles estimating the association between CEBPE rs2239633 polymorphism and childhood ALL risk. The pooled odds ratio (OR) with 95 % confidence intervals (CIs) were calculated. A significant association between CEBPE rs2239633 polymorphism with childhood ALL was found (OR = 1.19, 95 % CI 1.11-1.28, P < 0.01). Subgroup analysis stratified by ethnicity also suggested a significant association between this polymorphism and childhood ALL in the Caucasian subgroup (OR = 1.19, 95 % CI 1.09-1.30, P < 0.01) and Hispanic subgroup (OR = 1.39, 95 % CI 1.18-1.63, P < 0.01). No significant association was observed in the Asian subgroup (OR = 1.05, 95 % CI 0.90-1.22, P = 0.53). The CEBPE rs2239633 polymorphism increased B cell ALL risk (OR = 1.29, 95 % CI 1.15-1.44, P < 0.01) and B hyperdiploid ALL risk (OR = 1.84, 95 % CI 1.40-2.43, P < 0.01). This meta-analysis demonstrated that the CEBPE rs2239633 polymorphism was significantly associated with childhood ALL risk.

The evidence of an association between the Sulfotransferase 1A1 (SULT1A1) Arg213His polymorphism (rs9282861) and bladder cancer risk is still conflicting. We conducted a meta-analysis to assess the association between this polymorphism and bladder cancer risk.

Studies investigating the association between the BRCA1 rs799917 polymorphism and breast cancer risk have reported controversial results. In order to derive a more precise estimation of the relationship, we performed a comprehensive meta-analysis. A total of 8 articles comprising 19,878 subjects were included in this meta-analysis. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by Stata 11 software. Heterogeneity tests were conducted by Q test with I(2) value, and publication bias assessment was performed by Begg's funnel plot and Egger's test. The pooled results did not show any sufficient evidence approving the association between the BRCA1 rs799917 polymorphism and breast cancer risk in total population (T vs C: OR=1.01, 95% CI=0.97-1.06; TT vs CC: OR=1.03, 95% CI=0.93-1.13; CT vs CC: OR=1.04, 95% CI=0.92-1.16; TT+CT vs CC: OR=1.04, 95% CI=0.94-1.15; TT vs CT+CC: OR=1.03, 95% CI=0.94-1.12). In the further subgroup analyses, no significant associations were found in any comparison models according to ethnicity and source of controls. No publication bias was observed in this meta-analysis. In summary, based on the overall results, this meta-analysis strongly suggests that the BRCA1 rs799917 polymorphism is not associated with breast cancer risk.

The serine hydroxymethyltransferase (SHMT1) is the key enzyme in the folate metabolic pathway to provide one-carbon unit that plays an important role in biosynthesis. Abnormal biosynthesis involved in DNA synthesis and methylation can lead to activation of oncogenes and inactivation of tumor suppressor genes. And the abnormal biosynthesis is closely related to a variety of common tumors' occurrence and development. A SNP in SHMT1 C1420T may effect the procession of biosynthesis and finally influence cancer occurrence.

Recently, several molecular epidemiological studies have focused on the association between pri-miR-34b/c rs4938723 SNP and the susceptibility to different cancers. Due to the controversial rather than conclusive results, we performed this meta-analysis to assess more precise and comprehensive conclusion about the association. Data published until July 2014 were collected from PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Data, Chinese BioMedical Literature Database, and VIP database of Chinese Journal. Ultimately, 13 articles with a total of 7,753 cases and 8,014 controls were considered eligible for inclusion. The odds ratio (OR) and its 95 % confidence interval (95%CI) were used to assess the strength of association. In the overall analysis, a significant association between pri-miR-34b/c rs4938723 polymorphism and increased cancer susceptibility was found in heterozygous model (TC vs. TT: OR = 1.148, 95%CI 1.034-1.275, P = 0.010) and dominant model (CC + TC vs. TT: OR =1.166, 95%CI 1.028-1.322, P = 0.017). In subgroup analysis of ethnicity, pri-miR-34b/c rs4938723 polymorphism was significantly associated with an increased cancer susceptibility for Asian population in heterozygous model (TC vs. TT: OR = 1.169, 95%CI 1.031-1.326, P = 0.015) and dominant model (CC + TC vs. TT: OR = 1.185, 95%CI 1.017-1.382, P = 0.030), whereas no significant association for Caucasian population was observed in any genetic models. Intriguingly, stratified analysis revealed opposite results that pri-miR-34b/c polymorphism contributed to susceptibility to hepatocellular carcinoma while reduced susceptibility to colorectal cancer and esophageal squamous cell cancer in Asians. Considering some limitation of our meta-analysis, future well-designed case-control studies with larger sample sizes are required to confirm our findings.

Nuclear factor-kappa B (NF-κB), a cell survival signal, is involved in carcinogenesis. Polymorphism of NF-κB1 is associated with cancer by several studies. This study aims to perform a comprehensive meta-analysis of studies and determine the association between the NF-κB1-94ins/del ATTG promoter polymorphism and cancer. Twenty-five case-control studies (7,281 cases and 10,039 controls) were included. We used odds ratios (ORs) to assess the strength of the association, and 95 % confidence intervals (CIs) to identify precision of the estimate. Overall, NF-κB1-94ins/del ATTG promoter polymorphism was significantly associated with decreased susceptibility to cancer in overall population under homozygote (for DD vs. WW: OR = 0.74, 95 % CI = 0.58-0.96), recessive (for DD vs. WD+WW: OR = 0.82, 95 % CI = 0.69-0.99), dominant (for DD+WD vs. WW: OR = 0.84, 95 % CI = 0.71-1.00), and allele (for D vs. W: OR = 0.88, 95 % CI = 0.78-0.98) model. Subgroup analysis for ethnicity found that NF-κB1-94ins/del ATTG promoter polymorphism was significantly associated with decreased susceptibility to cancer in Asians (for DD vs. WW: OR = 0.54, 95 % CI = 0.40-0.74; for WD vs. WW: OR = 0.75, 95 % CI = 0.69-0.81; for DD vs. WD+WW: OR = 0.70, 95 % CI = 0.55-0.90; for DD+WD vs. WW; OR = 0.66, 95 % CI = 0.56-0.78; for D vs. W: OR = 0.75, 95 % CI = 0.65-0.86), but the association was not found in Caucasians. The findings suggest that NF-κB1-94ins/delATTG promoter polymorphism is significantly associated with decreased susceptibility to cancer in overall and Asian population.

EGF and its receptor EGFR serve as a paradigm for signaling in cell, molecular and tumor biology. EGFR inhibitors, drugs targeting the intracellular kinase activity and antibodies targeting the extracellular ligand binding, are used to treat breast, lung, colon and other cancers. Nominally affecting the same target, inhibitors have different effects, suggesting that use of inhibitor combinations may provide beneficial in cancer treatment. To explore the specific and the common transcriptional effects of EGFR inhibitors, we present metaanalysis of 20 individual studies comprising 346 microarrays. We identified specific gene subsets regulated by kinase inhibitors, those regulated using antibodies and by suppressing EGFR expression using miR-7. Unreported before, the inhibitors prominently induce lysosome components. All inhibitors rely on related sets of transcription factors and protein kinases, both for transcriptional induction and suppression. However, we find that Gefitinib suppresses apoptosis inhibitors, while inducing cell-cycle inhibitors; conversely, Erlotinib suppresses cell-cycle and cell migration genes, while inducing proapoptotic genes. EGFR-targeting antibodies specifically suppress cell motility, developmental and differentiation processes, while inducing the contractile apparatus. miR-7, distinctively, suppresses cell-cycle genes, while inducing transcription machinery. These metaanalysis results suggest that different inhibitors have overlapping but quite distinct effects in target cells. Judicial use of EGFR-targeting combinations, i.e., simultaneous use of antibodies and multiple kinase inhibitors, may provide more effective cancer treatments with fewer side-effects and avoid development of resistance. We expect, moreover, that specific drug combination treatments can be fine-tuned to achieve specific, personalized results.

Aberrant methylation of the global genome has been investigated as a prognostic indicator in various cancers, but the results are controversial and ambiguous.

It is still unclear whether or not rs498872 at 11q23.3 increases the risk of developing glioma, because the previous literature has reported mixed findings. We carried out a meta-analysis with an aim to test the hypothesis that rs498872 contributes to the development of glioma. Eligible studies were identified through databases including the Chinese biomedical literature database, China national knowledge infrastructure, Science Direct, Embase and PubMed. The risk of glioma (OR and 95% CI) was evaluated with the fixed-effects model or the random-effects model. Sensitivity analysis and publication bias tests were performed to check the reliability of our findings. Ten independent populations representing three ethnicities were analyzed in this study. We found 1.17-1.34-fold increased risk of glioma associated with rs498872 genotypes (OR 1.34, 95% CI 1.22-1.46; OR 1.24, 95% CI 1.14-1.35; OR 1.20, 95% CI 1.10-1.31; OR 1.17, 95% CI 1.08-1.27). In the stratified analysis by ethnicity, we also observed a significant increase in the risk of glioma in both Americans and Europeans. The results of our study support that the rs498872 polymorphism at 11q23.3 locus may be an important risk factor for glioma risk.

STAT4 is a latent cytosolic factor that encodes a transcription factor transmitting signals stimulated by cytokines. Previous studies with different study designs in diverse ethnic populations have assessed the influence of STAT4 rs7574865 polymorphism on HBV-induced HCC risk. The aim of the current study was to investigate the effects in a larger sample. The individual reports published up to Dec. 30, 2013 were systematically identified by searching the PubMed and Embase databases. To combine the OR and corresponding 95% CI, we used the fixed effects model during meta-analysis. Based on eight independent populations with a total of 5,719 cases and 6,525 controls, we found a slightly reduced risk of HBV-induced HCC in individuals with the minor T allele compared with individuals with the common G allele (T versus G: OR = 0.87, 95% CI = 0.82-0.91, P(Het) = 0.974). Similar reductions were also indicated in all subgroups. The combined data indicate that STAT4 rs7574865 polymorphism may be associated with significantly reduced risk of HBV-induced HCC in Asian.