Published studies researching the prognostic significance of ezrin expression in patients with osteosarcoma are inconclusive and heterogeneous. We conducted a meta-analysis to assess its prognostic value more precisely. The hazard ratios with corresponding 95 % confidence intervals were calculated to evaluate the effects. Five studies with 318 osteosarcoma patients were included to estimate the relationship between ezrin and disease-free survival, and ezrin and overall survival. Compared with osteosarcoma patients with low or negative ezrin expression, patients with high ezrin expression tended to be associated with lower disease-free survival, but the difference was not significant. However, patients with high ezrin expression were obviously associated with lower overall survival. Therefore, the findings from this systematic review suggest that ezrin expression is an effective biomarker of prognosis in patients with osteosarcoma.

Previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and clinical outcome of platinum-based chemotherapy in patients with lung cancer reported conflicting results. A meta-analysis was performed to provide a systematic review of the published data. We retrieved the relevant studies from PubMed and Embase databases. The primary outcome was overall survival, and the hazard ratio (HR) with 95% confidence interval (95% CI) was estimated. Seven studies with a total of 1,514 patients were included into the meta-analysis. Overall, XRCC3 Thr241Met polymorphism had no influence on the overall survival of lung cancer patients receiving platinum-based chemotherapy (MetMet vs. ThrThr: HR = 0.82, 95% CI 0.52-1.31, P = 0.410; MetThr vs. ThrThr: HR = 0.93, 95% CI 0.79-1.10, P = 0.339; MetMet/MetThr vs. ThrThr: HR = 1.07, 95% CI 0.88-1.31, P = 0.480). There was no obvious risk of publication bias. Therefore, currently available data suggest that there is no predictive effect of XRCC3 Thr241Met polymorphism on platinum-based chemotherapy in lung cancer patients.

The correlation between xeroderma pigmentosum group D (XPD) polymorphisms (Lys751Gln and Asp312Asn) and clinical outcomes of non-small cell lung cancer (NSCLC) patients, who received platinum-based chemotherapy (Pt-chemotherapy), is still inconclusive. This meta-analysis was aimed to systematically review published evidence and ascertain the exact role of XPD polymorphisms.

Glutathione S-transferase P1 (GSTP1) gene Ile105Val polymorphism has been suggested to be involved in the development of glioma. However, the results from the studies regarding the association between GSTP1 Ile105Val polymorphism and glioma risk have been inconsistent. Thus, we performed a meta-analysis to investigate this association. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated using random or fixed effects model. Nine studies with 2,078 cases and 3,970 controls were finally included into this meta-analysis. The results suggested there was no association between GSTP1 Ile105Val polymorphism and glioma risk under recessive model (OR = 1.138, 95%CI = 0.966-1.341, Pheterogeneity = 0.088, P = 0.123). Subgroup analyses by ethnicity showed there was also no association between GSTP1 Ile105Val polymorphism and glioma risk in mixed populations under recessive model (OR = 1.199, 95%CI = 0.928-1.549, Pheterogeneity = 0.060, P = 0.166) and Caucasian populations (OR = 1.097, 95%CI = 0.885-1.360, Pheterogeneity = 0.186, P = 0.398). In conclusion, the meta-analysis suggests that there is no association between GSTP1 Ile105Val polymorphism and glioma risk. However, more well-designed and larger studies are needed to further assess this association.

The impact of the Oncotype Dx (ODX) breast cancer assay on adjuvant chemotherapy (ACT) treatment decisions has been evaluated in many previous studies. However, it can be difficult to interpret the collective findings, which were conducted in diverse settings with limited sample sizes. We conducted a systematic review and meta-analysis to synthesize the results and provide insights about ODX utility. Studies, identified from PubMed, Embase, ASCO, and SABCS, were included if patients had ER+, node -, early-stage breast cancer, reported use of ODX to inform actual ACT decisions. Information was summarized and pooled according to: (1) distribution of ODX recurrence scores (RS), (2) impact of ODX on ACT recommendations, (3) impact of ODX on ACT use, and (4) proportion of patients following the treatment suggested by the ODX RS. A total of 23 studies met inclusion criteria. The distribution of RS categories was 48.8 % low, 39.0 % intermediate, and 12.2 % high (21 studies, 4,156 patients). ODX changed the clinical-pathological ACT recommendation in 33.4 % of patients (8 studies, 1,437 patients). In patients receiving ODX, receipt of ACT were: 28.2 % overall, 5.8 % low, 37.4 % intermediate, and 83.4 % high. Low RS patients were significantly more likely to follow the treatment suggested by ODX versus high RS patients RR: 1.07 (1.01–1.14) [corrected].The pooled results are consistent with most individual studies to date. The increased proportion of intermediate scores relative to original estimates may have implications for the clinical utility and cost impacts of testing. In addition, low versus high RS patients were significantly more likely to follow the ODX results, suggesting a tendency toward less aggressive treatment, despite a high ODX RS. Finally, there was a lack of studies on the impact of ODX on ACT use versus standard approaches, suggesting that additional studies are warranted.

Many studies have reported the role of xeroderma pigmentosum group D (XPD) with prostate cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. A total of 8 studies including 2620 cases and 3225 controls described Asp312Asn genotypes, among which 10 articles involving 3230 cases and 3582 controls described Lys751Gln genotypes and were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, a significant association between prostate cancer risk and XPD Asp312Asn polymorphism was found. For Asp312Asn polymorphism, in the stratified analysis by ethnicity and source of controls, prostate cancer risk was observed in co-dominant, dominant and recessive models, while no evidence of any associations of XPD Lys751Gln polymorphism with prostate cancer was found in the overall or subgroup analyses. Our meta-analysis supports that the XPD Asp312Asn polymorphism contributed to the risk of prostate cancer from currently available evidence. However, a study with a larger sample size is needed to further evaluate gene-environment interaction on XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk.

The Ena/VASP (enabled/vasodilator stimulated phosphoprotein) family includes the binding actin proteins such as mammalian Ena (Mena), VASP, and Ena-VASP-like. It is known that the perturbation of actin cycle could determine alteration in the mobility of cells and in consequence of organogenesis. Few recent studies have revealed that Mena protein could play a role in breast or pancreatic carcinogenesis. Based on our researches, we observed that the intensity of Mena expression increased from premalignant to malignant lesions in some organs such as large bowel, stomach, cervix, and salivary glands. These findings prove that Mena could be a marker of premalignant epithelial lesions. In premalignant lesions, it could be helpful to define more accurately the risk for malignant transformation. In malignant tumors, correlation of expression of its splice variants could indicate metastatic behavior. In conclusion, we consider that it is necessary to analyze the expression of Mena splice variants in a higher number of cases, in different epithelial lesions, and also in experimental studies to define its exact role in carcinogenesis and also its possible prognostic and predictive values.

X-ray repair cross-complementing protein 3 (XRCC3) is an essential gene involved in the double-strand break repair pathway. Published evidence has shown controversial results about the relationship between XRCC3 Thr241Met polymorphism and clinical outcomes of non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy.

In the present study we conducted a systematic review and meta-analysis of published data to quantify the impact of the DPYD IVS14+1G>A and 2846A>T variants on the risk of fluoropyrimidine-related toxicities and to determine sensitivity and specificity testing for DPYD variants.

Mutation of the p53 gene is a key event in the carcinogenesis of many different types of tumours. These can occur throughout the length of the p53 gene. Anti-p53 auto-antibodies are commonly produced in response to these p53 mutations. This review firstly describes the various mechanisms of p53 dysfunction and their association with subsequent carcinogenesis. Following this, the mechanisms of induction of anti-p53 auto-antibody production are shown, with various hypotheses for the discrepancies between the presence of p53 mutation and the presence/absence of anti-p53 auto-antibodies. A systematic review was performed with a descriptive summary of key findings of each anti-p53 auto-antibody study in all cancers published in the last 30 years. Using this, the cumulative frequency of anti-p53 auto-antibody in each cancer type is calculated and then compared with the incidence of p53 mutation in each cancer to provide the largest sample calculation and correlation between mutation and anti-p53 auto-antibody published to date. Finally, the review focuses on the data of anti-p53 auto-antibody in colorectal cancer studies, and discusses future strategies including the potentially promising role using anti-p53 auto-antibody presence in screening and surveillance.

Genetic polymorphisms in glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) genes have been widely reported and considered to have a significant effect on prostate cancer (PCa) risk, but the results are inconsistent. To evaluate the impact of the GSTM1 and GSTT1 polymorphism on PCa risk, we conducted a comprehensive meta-analysis based on 18 eligible studies. A total of 18 studies, including 7,119 subjects for GSTM1 and 6,454 subjects for GSTT1 between 1999 and 2012 were identified through researching MEDLINE, PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure database, and Chinese Biomedical Literature database. A meta-analysis was performed to obtain summary-estimated odd ratios and 95% confidence intervals of GSTM1 and GSTT1 polymorphisms for PCa, with attention to study quality and publication bias. Overall, there is a significant association between GSTM1 (odds ratio (OR) = 1.407, 95% confidence intervals (95% CI) = 1.147-1.727, I(2) = 73.2%, P = 0.001) genotypes and PCa susceptibility. Significant associations were also observed in subgroups of Caucasian populations (OR = 1.262, 95% CI = 1.055-1.511, I(2) = 48.7%, P = 0.011) and Asian populations (OR = 1.776, 95% CI = 1.134-2.781, I(2) = 83.4%, P = 0.012). However, no significant association was found (OR = 1.776, 95% CI = 1.134-2.781, P = 0.243) in African-American populations when stratified by ethnicity. While, there was no significant association seen between GSTT1 (OR = 1.003, 95% CI = 0.823-1.298, I(2) = 68.8%, P = 0.778) genotypes and PCa risk. However, no significant associations were observed in subgroups of Caucasian populations (OR = 1.086, 95% CI = 0.801-1.471, I(2) = 72.1%, P = 0.597) and Asian populations (OR = 0.961, 95% CI = 0.644-1.434, I(2) = 73.0%, P = 0.846), and similar result was found among African-American populations (OR = 0.802, 95% CI = 0.194-3.321, P = 0.761) when stratified by ethnicity. Our results suggest that the GSTM1 gene polymorphism contributes to PCa susceptibility, while GSTT1 gene polymorphism is not associated with PCa in our study.

Candidate gene and genome-wide association studies (GWAS) represent two complementary approaches to uncovering genetic contributions to common diseases. We systematically reviewed the contributions of these approaches to our knowledge of genetic associations with cancer risk by analyzing the data in the Cancer Genome-wide Association and Meta Analyses database (Cancer GAMAdb). The database catalogs studies published since January 1, 2000, by study and cancer type. In all, we found that meta-analyses and pooled analyses of candidate genes reported 349 statistically significant associations and GWAS reported 269, for a total of 577 unique associations. Only 41 (7.1%) associations were reported in both candidate gene meta-analyses and GWAS, usually with similar effect sizes. When considering only noteworthy associations (defined as those with false-positive report probabilities≤0.2) and accounting for indirect overlap, we found 202 associations, with 27 of those appearing in both meta-analyses and GWAS. Our findings suggest that meta-analyses of well-conducted candidate gene studies may continue to add to our understanding of the genetic associations in the post-GWAS era.

Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can be caused by either germline mutations in mismatch repair (MMR) genes, or non-inherited transcriptional silencing of the MLH1 promoter. A correlation between MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has been reported in CRC studies. Germline MMR mutations also greatly increase risk of endometrial cancer (EC), but no systematic review has been undertaken to determine if these tumour markers may be useful predictors of MMR mutation status in EC patients. Endometrial cancer cohorts meeting review inclusion criteria encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11 studies for MLH1 methylation testing. BRAF V600E mutations were reported in 4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were 7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15. Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in 48/51 (94%) of tumours. We have also detailed specific examples that show the importance of MLH1 promoter region, assay design, and quantification of methylation. This review shows that BRAF mutations occurs so infrequently in endometrial tumours they can be discounted as a useful marker for predicting MMR-negative mutation status, and further studies of endometrial cohorts with known MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter methylation as a marker of negative germline MMR mutation status in EC patients.

Numerous epidemiological studies have evaluated the association between the glutathione S-transferases P1 (GSTP1) Ile105Val polymorphisms and prostate cancer (PCa) risk. However, these studies have yielded conflicting results. A comprehensive search was conducted through researching MEDLINE, PubMed, Web of Science, and EMBASE, and a total of 13 studies including 3,227 cases and 3,945 controls were identified. A meta-analysis was performed to obtain a summary of estimated odds ratios (ORs) and 95% confidence intervals (CIs) of GSTP1 polymorphisms for PCa, with attention to study quality and publication bias. The GSTP1 Ile158Val variant genotypes are less associated with increased risk of PCa for the homozygote model (Val/Val vs Ile/Ile: OR = 1.42; I(2) = 63.7%; 95% CI = 1.02-1.97) and the recessive model (OR = 1.41; I(2) = 45.5%; 95% CI = 1.10-1.80). However, no associations were detected for other genetic models. In the stratified analysis by ethnicity, significant associations between GSTP1 Ile105Val polymorphism and PCa risk were also found among Caucasians for Val/Val vs Ile/Ile comparison (OR = 1.22; I(2) = 0.0 %; 95 % CI = 1.02-1.47) and for the recessive model (OR = 1.26; I(2) = 0.0%; 95% CI = 1.06-1.49), while there were no associations found for other genetic models. However, no associations were found in Asians and African-Americans for all genetic models when stratified by ethnicity. In conclusion, our meta-analysis provides evidence that GSTP1 Ile105Val gene polymorphisms contributed to PCa susceptibility.

The significance of KRAS in advanced colorectal cancer (CRC) treated with bevacizumab (B) is not well understood. We conducted a systematic review and pooled analysis of published trials with the aim to assess the predictive and prognostic role of KRAS status in patients treated with B. We performed a systematic search of PubMed, EMBASE, Web of Science, and Cochrane Register of Controlled Trials. The primary endpoints included objective response rate (RR), progression-free survival (PFS), and overall survival (OS). The odds ratio (OR) for RR and hazard ratios (HRs) were calculated or extracted by published data either using a fixed effect model or a random effect model. A total of 12 studies were included. A total of 2,266 patients were analysed (54 % were KRAS wt). The pooled RRs for KRAS wild-type (wt) versus mutated (mut) patients were 54.8 and 48.3 %, respectively (OR 1.42, P = 0.02). Median PFS was significantly longer in KRAS wt patients compared with that in KRAS mut patients (HR = 0.85; 95 % confidence interval (CI) 0.74-0.98; P = 0.02). Similarly, median OS was significantly better in wt KRAS patients compared with that in mut KRAS patients (HR = 0.65; 95 % CI 0.46-0.92; P = 0.01). This pooled analysis of 12 published studies shows that KRAS wt status is a good prognostic factor for B-based chemotherapy. Also, KRAS wt CRC is associated with a better RR with B plus chemotherapy than mut counterpart.

Numerous epidemiological studies have been conducted to explore the association between the Lys939Gln polymorphism of Xeroderma pigmentosum group C (XPC) gene and urinary bladder cancer susceptibility. However, the results remain inconclusive. In order to derive a more precise estimation of this relationship, a large and update meta-analysis was performed in this study.

Glutathione S-transferases (GSTs) enzymes are involved in conjugation of electrophilic compounds to glutathione, and glutathione S-transferase T 1 (GSTT1) and glutathione S-transferase M 1 (GSTM1) polymorphisms have been implicated as risk factors for prostate cancer. We conducted a systematic review and meta-analysis to define the effect of GSTM1 and GSTT1 null genotypes on prostate cancer risk in Asians. We searched the PubMed and Wanfang Medical databases to identify published case-control studies investigating the associations of GSTM1 and GSTT1 null genotypes with risk of prostate cancer in Asians. Heterogeneity was assessed using Cochran's Q statistic and odds ratios (OR) with corresponding 95 % confidence intervals (95 % CI) from individual studies were pooled using fixed or random effects models according to the heterogeneity. There were 18 studies (2,046 cases, 2,876 controls) on GSTM1 polymorphism, 15 studies (1,677 cases, 2,431 controls) on GSTT1 polymorphism, and 6 studies (675 cases, 853 controls) on GSTM1/GSTT1 interaction analysis. Overall, GSTM1 null genotype was significantly associated with increased risk of prostate cancer in Asians (random effects OR 1.80, 95 % CI 1.48-2.18, P < 0.001), and GSTT1 null genotype was also significantly associated with increased risk of prostate cancer in Asians (random effects OR 1.40, 95 % CI 1.10-1.80, P < 0.001). In addition, the GSTM1/GSTT dual null genotype was associated with higher risk of prostate cancer in Asians (random effects OR 2.14, 95 % CI 1.59-2.89, P = 0.007). In conclusion, GSTM1 and GSTT1 null genotypes are associated with increased risk of prostate cancer in Asians, and GSTM1 and GSTT1 null genotypes are risk factors for the development of prostate cancer.

Studies have examined whether tumor expression of PTGS2 (also known as COX-2), an enzyme inhibited by nonsteroidal anti-inflammatory drugs such as aspirin, is associated with prognosis in patients with colorectal cancer. However, results to date have been mixed.

Pertuzumab is a monoclonal antibody that represents the first among a new class of agents known as human epidermal growth factor receptor (HER) dimerization inhibitors. This is the first systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to synthesize all available data of pertuzumab in breast cancer. The search strategy retrieved 11 studies that evaluated pertuzumab. One study was conducted in the neoadjuvant setting (417 patients), whereas all the others dealt with patients with recurrent, metastatic, or refractory disease (1023 patients). Six studies were conducted in HER2(+) breast cancer population (1354 patients), whereas 5 studies (86 patients) were conducted in HER2(-) (or unknown HER2 status) disease. Pertuzumab is the most recent agent approved by the US Food and Drug Administration in combination with trastuzumab and docetaxel for the treatment of patients with HER2(+) metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. This approval has been based on data from a phase III Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study. The antitumor activity with the significant reduction in the risk of progression or death, as reflected upon the increase of 6.1 months in median progression-free survival, indicates that pertuzumab may provide an avenue for achieving additional benefit for patients with HER2(+). Moreover, pertuzumab seems to have a putative role in the management of patients with HER2 who are resistant to trastuzumab. The promising role of pertuzumab in the neoadjuvant and adjuvant settings remains to be further investigated and established in the future.

The prognostic value of p16 promoter hypermethylation in cancers has been evaluated for several years while the results remain controversial. We thus performed a systematic review and meta-analysis of studies assessing the impact of p16 methylation on overall survival (OS) and disease-free survival (DFS) to clarify this issue.