Previous studies have revealed that the expression level of microRNA-29a (miR-29a) was remarkably different in colorectal cancer (CRC) patients and healthy controls, indicating that miR-29a can be used as a diagnostic marker of CRC, but the results have been inconsistent. We conducted this meta-analysis to assess the diagnostic performance of blood-based miR-29a for CRC. We performed a systematic review of studies published over the past two decades to investigate the diagnostic performance of serum miR-29a for the diagnosis of CRC. QUADAS-2 was used to evaluate the quality of the studies. Performance characteristics (diagnostic sensitivity, specificity, and other measures of accuracy) were pooled and examined using random-effect models. Five studies, which included 281 CRC patients and 299 healthy controls, met the inclusion criteria. The summary estimates for miR-29a in CRC diagnoses showed a diagnostic sensitivity of 0.59 (95%CI = 0.53-0.65), a specificity of 0.89 (95%CI = 0.85-0.93), and a diagnostic odds ratio of 12.22 (95%CI = 5.07-29.44). The area under curve and Q value for the summary receiver operating characteristic curves were 0.9128 and 0.8453, respectively. In conclusion, miR-29a may be a novel potential biomarker for CRC diagnosis.

Consistency of procedures for the evaluation of a predictive biomarker (including sample collection, processing, assay and scoring system) based on adequate evidence is necessary to implement research findings in clinical practice. As a case study we evaluated how a particular predictive biomarker, ERCC1, was assessed in research on platinum-based chemotherapy in non-small-cell lung cancer and what motivated the choice of procedure.

To date, many studies have reported that microRNAs participate in human carcinogenesis as tumor suppressors or oncogenes and may play important roles as prognostic biomarkers of cancer. The aim of this meta-analysis was to assess the prognostic value of circulating miR-125 in human malignant neoplasms by summarizing the results from all available studies.

A DNA repair protein, X-ray repair cross-complementing group 1 (XRCC1), has been implicated in the development of multiple cancers, including non-Hodgkin lymphoma (NHL). Recent studies evaluating the association between XRCC1 polymorphisms and NHL risk have been published. However, the published studies are controversial. This systematic review and meta-analysis of case-control studies aimed to evaluate the association between three single nucleotide polymorphisms (SNPs) of XRCC1, Arg194Trp, Arg280His and Arg399Gln, with risk for developing NHL. We conducted a comprehensive literature search using PubMed, Embase, and the Cochrane Library databases for relevant studies regarding the association between XRCC1 SNPs and NHL risk. Thirteen published case-control studies involving the Arg194Trp (3897 cases and 5371 controls), Arg280His (2140 cases and 3158 controls) and Arg399Gln (2722 cases and 4856 controls) SNPs were selected for meta-analysis. The Arg194Trp SNP was associated with increased NHL risk within the Asian population, and increased diffuse large B cell lymphoma (DLBCL) risk within the overall population under dominant model. The Arg399Gln SNP was associated with decreased risk for NHL and DLBCL under heterozygous and dominant models of inheritance. The Arg280His SNP was not associated with NHL risk by overall or subgroup analyses.

Regular aspirin use has been associated with inhibition of the whole spectrum of colorectal carcinogenesis, including prevention of metastases and reduced total mortality in colorectal cancer. Preclinical data show that aspirin down-regulates PI3 kinase (PI3K) signalling activity through cyclo-oxygenase-2 (COX-2) inhibition, leading to the hypothesis that the effect of aspirin might be different according to PIK3CA mutational status, but epidemiological studies have led to conflicting results. The aim of this study was to assess the relationship between PIK3CA status and the efficacy of regular use of aspirin after diagnosis on overall survival in colorectal cancer patients.

Numerous individual studies evaluating the relationship between CD44V6 over-expression and prognostic impact in patients with osteosarcoma (OS) have yielded in conclusive results. This meta-analysis aimed to determine the value of cell adhesion molecule CD44V6 in prognosis of OS by conducting a systematic review and meta-analysis. A comprehensive search was conducted using PubMed (medline), Embase, ISI Web of Knowledge, Springer, the Cochrane Library, Scopus, BioMed Central, ScienceDirect, Wanfang, Weipu, and China National Knowledge Internet (CNKI) databases from inception through May 26, 2015. All available articles written in English or Chinese that investigated the expression of CD44V6 and the prognosis of OS were included. The quantity of the studies was evaluated according to the critical review checklist of the Dutch Cochrane Centre proposed by MOOSE. Finally, a total of eight studies with 486 OS patients were involved and the results indicated that the positive expression of CD44V6 predicts neoplasm metastasis (RR = 1.76, 95 % CI 1.38-2.25, p < 0.00001), and poor survival in OS with the pooled HR of 1.53 (95 % CI 1.25-1.88, p < 0.0001). No significant heterogeneity was observed among all studies. In conclusion, the present meta-analysis and systematic review strongly suggest that CD44V6 over-expression is associated with overall survival rate and metastasis in OS, and may be used as a prognostic biomarker to guide the clinical therapy for OS.

The germline R337H mutation of the TP53 gene has been associated with the development of many tumor types. This systematic review of literature investigated the association between the R337H mutation and the patients' family history and its predictive and prognostic value in cancer. Data were collected from articles archived in the PubMed, LILACS, MEDLINE, IBECS, and SciELO databases. The systematic review of literature was performed on 12 selected articles, describing a total of 175,462 individuals tested for the R337H mutation, including 1548 individuals with cancer and 118 individuals with a family history of Li-Fraumeni and Li-Fraumeni-like syndrome. Eight studies showed an association between the mutation and a family history of cancer in 411 patients, including 390 cases of cancer among family members. Patients with the homozygous mutant genotype experienced cancer recurrence, progressive disease, secondary cancer, and a short survival rate. Heterozygous patients showed a better response to treatment and increased survival rates than did patients with the homozygous mutant genotype from newborns to adult patients. In conclusion, the R337H mutation has significant predictive and prognostic value and is associated with tumorigenesis of the adrenal cortex.

The objective of this study was to perform a systematic review of the correlations between the single nucleotide polymorphism rs4680 in the catechol-O-methyltransferase (COMT) gene and susceptibility to ovarian cancer. A computer search was carried out for relevant case-control studies published between January 2000 to January 2014 in databases such as Ovid, EBSCO, PubMed, CNKI, CBMDISC, VIP, and WanFang Data. The literature was screened based on inclusion and exclusion criteria. A meta-analysis was performed by calculating the combined odds ratios (OR) and 95% confidence intervals (CI) using the RevMan 5.0. A total of 7 case-control studies were selected, which included 1439 cases and 2927 control subjects. Meta-analysis showed that the rs4680 polymorphism was not associated with ovarian cancer [GG vs (GA+AA): OR = 1.02, 95%CI = 0.88-1.19; G vs A allele: OR = 1.0, 95%CI = 0.90-1.11]. We, therefore, conclude that the COMT rs4680 polymorphism is not associated with susceptibility to ovarian cancer.

We integrated all the eligible studies and investigated whether the TNF-α 308G/A polymorphism correlates with urogenital cancer risk. Tumor necrosis factor-α (TNF-α) is a risk factor for some urogenital cancers; however, in prostate and bladder cancers the results are controversial. PubMed, EMBASE, Web of Science, the Cochrane Library, the Chinese Biomedical Literature Database, and the Wanfang Database were searched for all case-control studies on the relationship between the TNF-α 308G/A polymorphism and susceptibility to urogenital cancer between January 1994 and January 2015. The pooled odds ratio with 95% confidence interval was calculated to assess the associations. A total of 504 articles were found, 39 of which involved 11,613 cases and 12,542 controls that fulfilled the inclusion criteria. Overall, the TNF-α 308G/A polymorphism was significantly associated with the risk of urogenital cancer. In the subgroup analysis for different cancer types, significant associations were found in cervical cancer and urothelial carcinoma, while our meta-analysis indicated that there were no significant associations between the TNF-α 308G/A polymorphism and prostate, bladder, or renal cancers. When stratified by ethnicity, significant associations were observed in Caucasian populations, whereas no significant associations were found in African-Americans, Asians, or mixed populations. Furthermore, carriers of the -308A allele among the hospital-based case-control group were at a high risk of urogenital cancer. Our meta-analysis showed that the TNF-α 308G/A polymorphism was significantly associated with urogenital cancer risk, particularly in the Caucasian and hospital-based populations.

The polymorphism rs16754 of the WT1 gene has been described as a possible prognostic marker in different acute myeloid leukemia (AML) cohorts; however, it is not supported by all the studies. We performed the first meta-analysis evaluating the effect of this polymorphism upon the effectiveness of standard AML therapy. Fourteen cohort studies were included (3618 patients). Patients with the variant allele showed a significant higher overall survival (OS) at 5 years (OR:1.24, 95% CI: 1.06-1.45, P=0.007, with dominant model). WT1 did not influence complete remission, but a higher disease-free survival was observed with the variant allele. In the subgroup analysis, Caucasians, pediatric and patients treated with idarubicin and etoposide carrying the variant allele showed consistent results in OS, whereas patients with cytogenetically normal AML did not show differences. To verify the effect of this polymorphism upon other outcomes, studies in larger and multiracial populations are needed.

Interleukin (IL)-6 and the downstream Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway have previously been reported to be important in the development of colorectal cancer (CRC), and several studies have shown the relationship between the polymorphisms of related genes in this pathway with the risk of CRC. However, the findings of these related studies are inconsistent. Moreover, there has no systematic review and meta-analysis to evaluate the relationship between genetic variants in IL-6/JAK/STAT3 pathway and CRC susceptibility. Hence, we conducted a meta-analysis to explore the relationship between polymorphisms in IL-6/JAK/STAT3 pathway genes and CRC risk. Eighteen eligible studies with a total of 13,795 CRC cases and 18,043 controls were identified by searching PubMed, Web of Science, Embase, and the Cochrane Library databases for the period up to September 15, 2015. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were used to calculate the strength of the association. Our results indicated that IL-6 genetic variants in allele additive model (OR = 1.05, 95 % CI = 1.00, 1.09) and JAK2 genetic variants (OR = 1.40, 95 % CI = 1.15, 1.65) in genotype recessive model were significantly associated with CRC risk. Moreover, the pooled data revealed that IL-6 rs1800795 polymorphism significantly increased the risk of CRC in allele additive model in Europe (OR = 1.07, 95 % CI = 1.01, 1.14). In conclusion, the present findings indicate that IL-6 and JAK2 genetic variants are associated with the increased risk of CRC while STAT3 genetic variants not. We need more well-designed clinical studies covering more countries and population to definitively establish the association between genetic variants in IL-6/JAK/STAT3 pathway and CRC susceptibility.

The CXC chemokine receptor 4 (CXCR4) has been reported to be involved in the development and progression of nasopharyngeal carcinoma (NPC). However, the role of CXCR4 in clinical outcome and prognosis of NPC patients remains controversial. In the present study, we investigated and reviewed the expression of CXCR4 in NPC tissues and then analyzed the definitive role of CXCR4 in clinical outcome and prognosis. Here, we found that the expression level of CXCR4 was significantly higher in NPC cancer specimens (61/98) than that in paired non-tumor tissues (p < 0.001). Together with our pathological analysis, statistic analysis revealed that CXCR4 expression was indeed closely correlated with UICC stage (p = 0.000), N stage (p = 0.019), and metastasis (p = 0.000). Most importantly, the systematic review combined with our survival and multivariate analysis that revealed high expression of CXCR4 was obviously associated with poor overall survival (OS) (p = 0.000) and progression-free survival (PFS) (p = 0.000) and can act as an independent prognostic factor in NPC patients. In conclusion, this study suggests that CXCR4 is highly activated and expressed in the development of NPC and may be recommended as an indicator in the diagnosis of NPC. Thus, targeting of CXCR4 gene or protein could be used as a potential therapy for NPC.

The best-known cause of intolerance to fluoropyrimidines is dihydropyrimidine dehydrogenase (DPD) deficiency, which can result from deleterious polymorphisms in the gene encoding DPD (DPYD), including DPYD*2A and c.2846A>T. Three other variants-DPYD c.1679T>G, c.1236G>A/HapB3, and c.1601G>A-have been associated with DPD deficiency, but no definitive evidence for the clinical validity of these variants is available. The primary objective of this systematic review and meta-analysis was to assess the clinical validity of c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity.

our aim was to evaluate whether somatic mutations in five genes were associated with an early age at presentation of breast cancer (BC) or serous ovarian cancer (SOC).

The micronucleus assay in uncultured exfoliated buccal mucosa cells, involving minimally invasive sampling, was successfully applied to evaluate inhalation and local exposure to genotoxic agents, impact of nutrition and lifestyle factors. The potential use of the assay in clinics to monitor the development of local oral lesions and as an early biomarker for tumors and different chronic disorders was also investigated. A systematic review of the literature was carried out focusing on the clinical application of the assay. The literature search updated to January 2015 allowed to retrieve 42 eligible articles. Fifty three percent of investigations are related to oral, head and neck cancer, and premalignant oral diseases. Our analysis evidences a potential usefulness of the MN assay applied in buccal exfoliated cells in the prescreening and in the follow up of precancerous oral lesions. A significant excess of MN, in patients compared with matched controls was observed for subgroups of oral and neck cancer (meta-MR of 2.40, 95% CI: 2.02-2.85) and leukoplakia (meta-MR 1.88, 95% CI: 1.51-2.35). The meta-analysis of studies available on other tumors (meta-MR 2.00; 95% CI:1.66-2.41) indicates that the MN frequency in buccal cells could reflect the chromosomal instability of other organs. Increased MN frequency was also observed in small size studies on patients with chronic diseases, with Alzheimer's disease and with Down syndrome. The application of the cytome approach providing information of genotoxic, cytotoxic and cytostatic effects is suggestive of the possibility of an improvement in the predictive value of the assay and this deserves further investigations.

Observational studies have reported controversial results on the association between GSTT1 and GSTM1 genotypes and treatment outcome of breast cancer. The purpose of this study is to evaluate the association between GSTT1 and GSTM1 and treatment outcome in breast cancer patients. Eligible studies were searched in PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases. A random-effect model or fixed-effect model was used to calculate the overall combined risk estimates. Twenty-one studies with a total of 4990 patients were included in this meta-analysis. The GSTM1 null genotype (odds ratio (OR) = 1.33, 95 % confidence interval (CI) 1.01-1.75, P = 0.046) and GSTT1/GSTM1 double null genotype (OR = 2.22, 95 % CI 1.02-4.84, P = 0.045) were significantly associated with an increased tumor response. A reduced overall survival (hazard ratio (HR) = 0.84, 95 % CI 0.72-0.98, P = 0.024) was observed in GSTM1 null genotype, especially in mixed descent (HR = 0.77, 95 % CI 0.61-0.96, P = 0.018) and large sample size (HR = 0.85, 95 % CI 0.72-0.99, P = 0.033). Evidence of publication bias was observed in GSTM1 genotype rather than in GSTT1 genotype. This meta-analysis suggests that GSTM1 null and GSTT1/GSTM1 double null polymorphisms might be significantly associated with an increased tumor response. However, the GSTM1 null genotype might be significantly associated with a reduced overall survival. Future studies are warranted to confirm these findings.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib or gefitinib are indicated for the treatment of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase domain mutations have been reported to be associated with EGFR-TKI response in patients with NSCLC. Certain patient subgroups in which EGFR somatic mutations are more frequently observed are thought to derive more clinical benefit from EGFR-TKI therapy. We performed a systematic review and meta-analysis to summarize the evidence regarding the association of smoking status with overall survival (OS) and progression-free survival (PFS) in patients with NSCLC receiving EGFR-TKI therapy with erlotinib or gefitinib.

To summarize the current evidence on the biomarkers associated with DNA methylation in the screening and diagnosis of colorectal cancer (CRC).

We conducted a meta-analysis of case-controlled prospective or retrospective studies to assess the effect of MTHFR polymorphisms on the risk of developing endometrial cancer.