To date, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may play an important role as prognostic biomarker of cancers. The present meta-analysis summarizes the recent advances in the use of microRNA-21 (miR-21) in the assessment of colorectal cancer and analyzes the prognostic role of miR-21 for survival outcome.

Perturbations in cell cycle and DNA repair genes might affect susceptibility to cancer. The aim of this meta-analysis is to generate large-scale evidence to determine the degree to which common Cyclin D1 (CCND1) G870A (dbSNP: rs603965) and xeroderma pigmentosum group C (XPC) Ala499Val (dbSNP: rs2228000) polymorphisms are associated with susceptibility to bladder cancer. The electronic databases PubMed, Embase, Web of Science, and CNKI were searched for relevant studies (with an upper date limit of July 25, 2013). The principal outcome measure for evaluating the strength of association was crude odds ratios (ORs) along with their corresponding confidence intervals (95%CIs). We found and reviewed nine case-control studies on CCND1 G870A with a total of 6,823 subjects and seven studies on XPC Ala499Val with a total of 7,674 subjects. Our meta-analysis provides evidence that the variant genotype of CCND1 G870A showed a significant association in the occurrence of invasive bladder tumors in former and current smokers. The XPC Ala499Val polymorphism correlated with significant differences between patients and unaffected subjects, but when the groups were stratified by ethnicity, the magnitude of the overall effect was similar only among Caucasian populations. Results from our meta-analysis support the view that the G870A polymorphism may modulate the risk of bladder cancer in conjunction with tobacco smoking and that the Ala499Val polymorphism may contribute to the susceptibility to bladder cancer in Caucasian populations. Our findings, however, warrant larger well-designed studies to investigate the significance of these two polymorphisms as markers of susceptibility to bladder cancer.

A HOXB13-to-IL17BR expression ratio was previously identified to predict a clinical outcome of breast cancer patients treated with adjuvant tamoxifen. A large number of studies were addressed to confirm its function as a predictor of breast cancer outcome treated with tamoxifen. However, conflicting results were got. In this study, a systematic search of databases was carried out, and other relevant papers were also identified. Then, the analyses were conducted according to the PRISMA and MOOSE guidelines. After full review, 11 studies with a total of 2,958 participants were deemed eligible and were included in the study. Pooled results revealed that women with higher HOXB13-to-IL17BR expression ratio had significantly worse outcomes in breast patients treated with tamoxifen, especially for those who are negative of node.

Methionine synthase reductase (MTRR) is required for the reductive methylation of cobalamin, which is the functional cofactorial form of methionine synthase (MS) in the remethylation of homocysteine to methionine. The MTRR A66G (rs1801394) polymorphism is found to be associated with decreased enzyme affinity for MTR, the gene that encodes MS, and has been widely investigated for cancer risk, including leukemia. However, the conclusions of epidemiological studies have always been contradictory. To further clarify the association of MTRR A66G polymorphism with the risk of leukemia, this meta-analysis was performed for 2913 cases and 4764 controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Pooled ORs were determined for the co-dominant model (GG vs. AA, AG vs. AA), dominant model (GG + AG vs. AA) and recessive model (GG vs. AA+ AG), respectively. No significant associations were found for all comparisons in the overall pooled analysis. However, the results of stratified analyses revealed that MTRR A66G GG genotype was associated with decreased leukemia risk in the Caucasian population, in children and for acute lymphoblastic leukemia (ALL). In contrast, increased risk was observed in the Asian population and for acute myeloid leukemia (AML). This meta-analysis suggests that MTRR A66G GG is associated with decreased risk of leukemia in a Caucasian population and in children, especially for ALL.

HIF-1 activates various genes in cancer progression and metastasis. HIF-1α 1772 C/T and 1790 G/A polymorphisms are reportedly associated with cancer risk; however, the results are inconclusive.

TP53 gene is one of the most important tumor suppressor genes. We undertook this meta-analysis to explore the association between TP53 Arg72Pro polymorphism and the risk of skin cancer mainly in Caucasians.

Xeroderma pigmentosum group D (XPD) is an essential gene involved in the nucleotide excision repair (NER) pathway. Two commonly studied single nucleotide polymorphisms (SNPs) of XPD (Lys751Gln, A>C, rs13181; Asp312Asn, G>A, rs1799793) are implicated in the modulation of DNA repair capacity, thus related to the responses to platinum-based chemotherapy. Here we performed a meta-analysis to better evaluate the association between the two XPD SNPs and clinical outcome of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients.

A common genetic variant, telomerase reverse transcriptase (TERT) rs2736098, was recently reported to be associated with lung cancer risk in Caucasians. In addition, many studies have investigated the role of this polymorphism in the etiology of cancer of various organs. Nevertheless, the results of related case-control studies remain inconsistent.

The inactivation of BRCA1 by epigenetic alterations is a critical event in breast tumorigenesis, which may potentially be used as a prognostic marker for patients with breast cancer. The present study systematically reviewed the promoter methylation of BRCA1 and its relationship to the clinical outcomes of breast cancer patients. We performed a meta-analysis following the PRISMA guideline. Relevant articles were identified by searching PubMed, Web of Science and Embase database until August 2013. The pooled hazard ratio (HR) and 95 % confidence interval (CI) were applied to estimate the effect of BRCA1 methylation. Random or fixed effect model was chosen based on the heterogeneity analysis. A total of 3,205 patients from nine eligible studies were included in the meta-analysis. BRCA1 methylation was found to be significantly correlated with a poor overall survival of breast cancer, with the combined HR (95 % CI) of 2.02 (1.35-3.03). After adjusting for potential confounders using the Cox regression model, the pooled HR (95 % CI) of BRCA1 methylation on patients' overall survival was 1.38 (1.04-1.84). If we used the disease-free survival as the outcome, the combined HR (95 % CI) was 2.89 (1.73-4.83) for univariate analysis and 3.92 (95 % CI 1.49-10.32) for multivariate analysis, respectively. Subgroup analysis of specimen types revealed that the pooled HR (95 % CI) for overall survival was 1.48 (1.22-1.81) when using formalin-fixed paraffin-embedded (FFPE) specimen and 1.38 (0.16-11.84) when using fresh frozen tissues. As for the disease-free survival, the pooled HR (95 % CI) was 2.47 (1.33-4.58) when using FFPE specimen and 2.78 (1.47-5.28) when using fresh frozen tissues. As a conclusion, the present meta-analysis provides evidence that BRCA1 methylation is associated with a poor survival of breast cancer patients. Our findings underscore the clinical relevance of aberrant epigenetic alteration as a promising biomarker for the prognosis of human cancers.

Many epidemiological studies have evaluated the association between microRNA-499 rs3746444 A/G polymorphism and cancer risk, but published data are still inconclusive. Therefore, we performed a meta-analysis to evaluate the association between microRNA-499 rs3746444 A/G polymorphism and cancer susceptibility. The summary odds ratio (OR) with its 95% confidence interval (CI) was calculated to evaluate the association. Seventeen case-control studies with a total of 7,974 cancer cases and 9,404 controls were finally included into this meta-analysis. Overall, microRNA-499 rs3746444 A/G polymorphism was significantly associated with increased risk in both the domain model (GG/AG versus AA: OR = 1.17, 95% CI, 1.03-1.33, P = 0.02) and the heterozygote comparison model (AG versus AA: OR = 1.15, 95% CI, 1.01-1.32, P = 0.03) when all studies were pooled into the meta-analysis. Subgroup analysis by ethnicity showed that association between microRNA-499 rs3746444 A/G polymorphism and cancer susceptibility was significant in Asians, but not in Caucasians. In the subgroup analysis by cancer types, no risk of breast, liver, or lung cancers were found significantly associated with microRNA-499 rs3746444 A/G polymorphism in any of the genetic models. In summary, this meta-analysis suggests that microRNA-499 rs3746444 A/G polymorphism is associated with increased susceptibility to cancer in Asians. However, more well-designed studies with large sample size are needed to validate this association among different kinds of cancers.

Recent studies have shown that microRNAs (miRNA) exhibit altered expression levels in cancers, and they may be considered as valuable prognostic biomarkers for patients with cancers. We performed this meta-analysis to provide a comprehensive evaluation of the role of miRNA-100 expression on the overall survival rate by calculating the pooled hazard ratio (HR) for overall survival (OS), which compared the high and low expression levels of miR-100 in patients of the available studies. Finally, a total of six studies dealing with various carcinomas were involved for this meta-analysis. The results indicated that lower expression of miR-100 in cancerous tissue could significantly predict poorer survival in various carcinomas with the pooled HR of 2.19 (95% CI 1.49-3.24, P = 0.0007). In conclusion, the findings from this present meta-analysis suggest that miR-100 expression is associated with OS in cancer patients and could be a useful clinical prognostic factor for those patients.

The Arg399Gln polymorphism, located in the region of the BRCT-I interaction domain of XRCC1, has been extensively explored in its function and association with glioma risk. However, these studies generated contradictory instead of conclusive results. A meta-analysis was performed to derive a more precise evaluation of the relationship between XRCC1 Arg399Gln polymorphism and glioma risk. We searched the PubMed, EMBASE, and Web of Science and extracted 12 eligible studies with 4,062 glioma cases and 5,302 glioma-free controls for this meta-analysis. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the association. In the overall analysis, we found that the XRCC1 Arg399Gln polymorphism was statistically associated with the risk of glioma (OR(GG vs. AG + AA) = 0.90, 95% CI = 0.84-0.97, P(heterogeneity) = 0.020; OR(allele G vs. allele A )= 0.96, 95% CI = 0.91-1.00, P(heterogeneity) = 0.110). We also observed significant association between this polymorphism and glioma risk in Asian populations. The results of the meta-analysis suggest a potential decreased susceptibility to glioma in association with the XRCC1 Arg399Gln polymorphism, especially in Asians. Yet, it is necessary to conduct future prospective explorations to gain a better insight into the impact of XRCC1 Arg399Gln polymorphism on glioma risk.

While the ERCC1 C8092A and ERCC2 K751Q polymorphisms have received much attention for their potential associations with adult glioma risk, inferences from such studies are hindered by their limited statistical power and conflicting results. The aim of this meta-analysis is to provide a relatively comprehensive account of the association between these two polymorphisms and adult glioma risk. A literature search for eligible studies published before September 1, 2013 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and CNKI databases. Pooled odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were used to evaluate the strength of the association under a fixed or random effect model according to heterogeneity test results. All analyses were performed using STATA software, version 12.0. Ten case-control studies were included in this meta-analysis, with a total of 5,843 adult glioma patients and 8,139 healthy controls. For ERCC1 C8092A (dbSNP: rs3212986, C>A), the combined results show that carriers of the AA genotype may be associated with a higher risk of adult glioma than carriers of the CA and CC genotypes. Stratified analyses show that the magnitude of the effect was especially significant among Asians, indicating ethnicity differences in adult glioma susceptibility. For ERCC2 K751Q (dbSNP: rs13181, A>C), the pooled ORs were not significant in the overall population, although all of the ORs were greater than 1. However, Asians seem to be significantly more susceptible to adult glioma than Caucasians. The results of this meta-analysis indicate that the AA genotype of ERCC1 C8092A may be associated with a higher risk of adult glioma than the CA and CC genotypes and that the risk allele of ERCC2 K751Q confers a significant susceptibility to adult glioma, especially in Asian populations. These polymorphisms may be used along with other genetic markers to identify individuals at high risk for adult glioma.

To derive a more precise estimation of the relationship between TGF-β1 polymorphisms and gastric cancer (GC) risk, we conducted a meta-analysis of all available case-control studies relating the C-509 T, T869C, and G 915C polymorphisms of the TGF-β1 gene to the risk of developing GC. The effect summary odds ratio (OR) and 95% confidence intervals (CIs) were obtained. Funnel plots and Egger's test were used to estimate publication bias. Finally, 11 studies were included in the final meta-analysis. With respect to C-509 T polymorphism, it was found that significantly increased GC risk was associated with the TT genotype in the recessive genetic model in overall analysis (TT vs. CC + CT: OR = 1.23, 95% CI 1.09-1.38, P(heterogeneity) = 0.13) and in Asian population (TT vs. CC + CT: OR = 1.24, 95% CI 1.10-1.39, P(heterogeneity) = 0.18). With respect to T869C and G915C polymorphisms, no significant association with GC risk was demonstrated in overall analysis and subgroup analyses according to ethnicity for all genetic models. This meta-analysis suggested that the T allele of TGF-β1 509C/T polymorphism is probably the susceptibility factor for GC.

Several genome-wide association studies on lung cancer (LC) have reported similar findings of a new susceptibility locus, 15q25. After that, a number of studies reported that rs8034191 and rs1051730 polymorphisms at chromosome 15q25 have been implicated in LC risk. However, studies have yielded contradictory results. To derive a more precise estimation of the relationship, a meta-analysis of 43,742 LC cases and 58,967 controls from 17 published case-control studies was performed. Overall, significantly elevated LC risk was associated with rs8034191-C (OR = 1.26, 95% CI 1.22-1.31, P < 10(-5)) and rs105173-A variant (OR = 1.28, 95% CI 1.20-1.36, P < 10(-5)) when all studies were pooled into the meta-analysis. In the subgroup analysis by ethnicity, significantly increased risks were found for rs8034191 and rs105173 polymorphisms among Caucasians and African American, while no significant associations were observed for the two polymorphisms in East Asians. In addition, we found that rs8034191 and rs105173 confer risk, for both adenocarcinoma and squamous cell carcinoma when stratified by histological types of LC. Furthermore, our results on stratified analysis according to smoking status showed an increased LC risk in ever-smokers, while no associations were detected among never-smokers for the two polymorphisms. In conclusion, this meta-analysis demonstrated that the two common variations (rs8034191 and rs1051730) at 15q25 are a risk factor associated with increased LC susceptibility, but these associations vary in different ethnic populations.

Genetic polymorphism of X-ray repair crosscomplementing group 3 (XRCC3) Thr241Met has been implicated to alter the risk of ovarian cancer, but the results are controversial. In order to get a more precise result, a meta-analysis was performed. All eligible studies were identified through an extensive search in PubMed, Excerpta Medica Database (Embase), Chinese National Knowledge Infrastructure database, and Chinese Biomedical Literature Database before August 2013. The association between the XRCC3 Thr241Met polymorphism and ovarian cancer risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). Finally, a total of four publications including seven studies with 3,635 cases and 5,473 controls were included in our meta-analysis. Overall, there was no association between XRCC3 Thr241Met polymorphism and risk of ovarian cancer under all five genetic models in overall population (T vs. C: OR = 0.99, 95 % CI = 0.960-1.03, P = 0.752; TT vs. CC: OR = 1.00, 95% CI = 0.91-1.10, P = 0.943; TC vs. TT: OR = 0.97, 95% CI = 0.92-1.04, P = 0.396, Fig. 1; TT vs.

MicroRNAs are involved in several biological processes including cell apoptosis and proliferation, stress resistance, and fat metabolism, and act as tumor suppressors by malignant transformation of human cells. The aim of this study was to identify the associations of single nucleotide polymorphisms (SNPs) rs11614913 and rs3746444 with lung cancer risk. In this meta-analysis with 2,219 cases and 2,232 controls for SNP rs11614913 and 1,685 cases and 1,690 controls for SNP rs3746444, we summarized five case-control studies by searching databases of PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI). Lung cancer risk associated with the two SNPs was estimated by odd ratios (ORs) with 95% confidence intervals (CIs). SNP rs11614913 (OR 0.88, 95% CI 0.78-1.00 for TT vs. CT + CC) was found to be potentially associated with a decreased risk of lung cancer. However, we found no association between SNP rs3746444 and lung cancer risk. In the subgroup analysis by ethnicity, a negative association was also observed in Asians for SNP rs11614913, but a nonsignificant association for SNP rs3746444. Our meta-analysis provides evidence for potential protective effects on lung cancer risk associated with SNP rs11614913, particularly in Asian populations. Further, larger studies are necessary to validate the findings.

Published data regarding the association between the APE1 Asp148Glu polymorphism and colorectal cancer susceptibility remained controversial. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship.

It has been suggested that the serine/threonine kinase 15 (STK15) T91A rs2273535 polymorphism is associated with susceptibility to cancer. However, the results are conflicting. We performed this meta-analysis to derive a more precise estimation of the relationship.

Glutathione S-transferases (GSTs) are a family of multifunctional enzymes that are involved in the metabolism of many xenobiotics, including a wide range of environmental carcinogens. While the null genotypes in GSTM1 and GSTT1 have been implicated in tumorigenesis, it remains inconsistent and inconclusive. Herein, we aimed to assess the possible associations of the GSTM1 and GSTT1 null genotype in cancer risks.