EGFR mutation might be a predictive factor for applying EGFR-tyrosine kinase inhibitors (EGFR-TKIs, including gefitinib, erlotinib and afatinib) in non-small-cell lung cancer (NSCLS) patients. Thus, it is necessary to pool previous trials to compare the effect of EGFR-TKIs versus cytotoxic chemotherapy in EGFR mutation positive (mut+) and negative (mut-) patients.

Numerous studies have evaluated the association between the X-ray repair cross-complementing group 1 (XRCC1) DNA repair gene polymorphism -77T>C and lung cancer risk. However, this association is controversial. We used PubMed and Embase to identify 5 case-control studies, which included 2488 lung cancer cases and 2576 controls, for inclusion in a comprehensive meta-analysis in order to assess this association. Two independent reviewers extracted data from the studies, and ORs with 95%CIs were calculated. When all studies were pooled, we found a significant association between the -77T>C polymorphism and lung cancer risk (TT vs CC: OR = 0.52, 95%CI = 0.34-0.80, P = 0.49; TT vs CT: OR = 0.71, 95%CI = 0.62-0.81, P = 0.69; dominant model: OR = 1.45, 95%CI = 1.27-1.66, P = 0.64; recessive model: OR = 0.54, 95%CI = 0.36-0.82, P = 0.24). In a subgroup analysis of nationalities, the -77T>C polymorphism was significantly associated with lung cancer risk in Asian patients. In conclusion, the XRCC1 -77T>C polymorphism might be related to increased risk of lung cancer in Asians. Future studies are needed for conclusive evidence about this association.

We examined whether the X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism is a risk factor for bladder cancer by conducting a meta-analysis. We searched the Pubmed and Embase databases for study retrieval. This meta-analysis examined 16 case-control studies, including 892 prostate cancer cases and 1020 healthy controls. Meta-analysis results based on these studies showed no significant association between the XRCC1 Arg399Gln polymorphism and bladder cancer risk in comparisons of the glutamine (Gln) allele vs arginine (Arg) allele, Arg/Arg vs (Gln/Gln + Gln/Arg), Gln/Gln vs (Gln/Arg + Arg/Arg), Gln/Gln vs Arg/Arg, and Gln/Arg vs Arg/Arg [odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.80-1.16, P = 0.70; OR = 1.13, 95%CI = 0.70-1.82, P = 0.62; OR = 0.92, 95%CI = 0.79-1.07, P = 0.29; OR = 0.90, 95%CI = 0.69-1.16, P = 0.42; OR = 0.89, 95%CI = 0.75-1.05, P = 0.17, respectively]. In subgroup analysis by ethnicity, no association was observed between the XRCC1 Arg399Gln polymorphism and bladder cancer risk in Caucasian, Mongoloid, or black populations. We identified no association between the XRCC1 Arg399Gln polymorphism and bladder cancer risk.

Numerous studies have evaluated the association between the X-ray repair cross-complementing group 3 (XRCC3) T241M polymorphism and lung cancer risk; however, the actual association is controversial. We examined whether the T241M polymorphism confers a lung cancer risk in China. We searched the PubMed, Google Scholar, and China National Knowledge Infrastructure databases to identify studies that examined the association between the XRCC3 T241M polymorphism and the risk of lung cancer. We estimated the pooled odds ratio with its 95% confidence interval to assess this association. A total of 3977 patients with lung cancer and 3761 controls from 8 comparative studies were included in this meta-analysis. The meta-analysis results revealed no significant association between the XRCC3 T241M polymorphism and lung cancer risk. In the subgroup analysis, 6 studies with sample sizes over 500 found that the T241M polymorphism had no association with lung cancer. The XRCC3 T241M polymorphism may not be a risk factor for lung cancer. However, larger studies involving a stratified case-control population and biological characterization are needed to validate this finding.

The purpose of this articles is to determine whether the cytochrome P450 2E1 (CYP2E1) Rsa I/Pst I gene polymorphism is correlated with respiratory system cancers. Respiratory system cancers included lung cancer, laryngeal cancer, nasopharyngeal cancer, and cancers of other respiratory organs, which are the most common malignant tumors worldwide; the significant relationship between CYP2E1 Rsa I/Pst I gene polymorphism and some respiratory system cancer have been reported, but results of some other studies are controversial. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the association. PubMed, EMBASE, Cochrane Library Databases, China National Knowledge Infrastructure, and Wanfang Database (up to July 20, 2014) were searched for all case-control studies those mainly studied the relationship between CYP2E1 Rsa I/Pst I gene polymorphism and the susceptibility of respiratory system cancer. A total of 332 articles were collected, among which 34 studies that involved 7028 cases and 9822 controls fulfilled the inclusion criteria after being assessed by 2 reviewers. When stratified by cancer site, the C2/C2 polymorphism could increase the risk of nasopharyngeal cancer under the homozygote model (C2C2 vs C1C1: OR = 1.85, 95% CI = 1.20-2.85, P = 0.005) and recessive model (C2C2 vs C1C2/C1C1: OR = 1.89, 95% CI = 1.23-2.89, P = 0.003). Protection effect was found in lung cancer in heterozygote model (C1C2 vs C1C1: OR = 0.82, 95% CI = 0.74-0.91, P < 0.001), dominant model (C1C2/C2C2 vs C1C1: OR = 0.83, 95% CI = 0.76-0.90, P < 0.001), and allele contrast model (C2 vs C1: OR = 0.85, 95% CI = 0.73-1.00, P = 0.045). With regard to ethnicity subgroup analysis, there was significant association in Asian population in heterozygote model (C1C2 vs C1C1: OR = 0.85, 95% CI = 0.78-0.94, P = 0.001), dominant model (C1C2/C2C2 vs C1C1: OR = 0.88, 95% CI = 0.81-0.95, P = 0.001), and recessive model (C2C2 vs C1C2/C1C1: OR = 1.25, 95% CI = 1.01-1.53, P = 0.036). CYP2E1 Rsa I/Pst I gene polymorphism may reduce the risk of respiratory system cancer. Furthermore, significant association was also found in Asian populations.

Increasing number of studies focused on the association of IL-17A rs2275913 and IL-17F rs763780 polymorphisms with gastric cancer (GC) risk. However, the results were inconsistent. To elucidate the exact association, we performed the present meta-analysis. Databases including PubMed, Web of knowledge and Chinese National Knowledge Infrastructure (CNKI) were systematically searched for potentially eligible literatures. Odds ratios (OR) and their 95% confidence interval (CI) were used to evaluate the strength of association. Eight studies for IL-17A rs2275913 (3345 cases and 4427 controls) and five studies for IL-17F rs763780 (1784 cases and 2592 controls) were finally included. The results indicated that individuals with AA genotype of IL-17A rs2275913 polymorphism were associated with increased GC risk compared with wild-type GG (OR=1.61, 95% CI=1.17-2.23, P=0.004); A allele was significantly associated with increased GC risk compared with G allele (OR=1.22, 95% CI=1.06-1.41, P=0.007). IL-17F rs763780 polymorphism was also significantly associated with increased GC risk (CC vs. CT: OR=1.40, 95% CI=1.04-1.88, P=0.025; CT vs. TT: OR=1.35, 95% CI=1.16-1.58, P<0.001; C allele vs. T allele: OR=1.30, 95% CI=1.15-1.47, P<0.001). In summary, IL-17A rs2275913 A/G polymorphism and IL-17F rs763780 C/T polymorphism might be associated with increased GC risk in Asians. Further large-scale studies are still required to confirm the results of this meta-analysis.

HIF-1 (hypoxia-inducible factor 1) is a transcriptional activator that functions as a critical regulator of oxygen homeostasis. Recently, a large number of epidemiological studies have investigated the relationship between HIF-1α C1772T/G1790A polymorphisms and cancer susceptibility. However, the results remain inconclusive. Therefore, we performed a meta-analysis on all of the available case-control studies to systematically summarize the possible association.

Women with BRCA1 and BRCA2 mutation carriers are at substantially elevated risk of developing ovarian cancer. The aim of the meta-analysis is to clarify the role of risk-reducing salpingo-oophorectomy (RRSO) to reduce ovarian cancer risk and mortality in women with BRCA 1 and BRCA 2 mutation carriers.

The aim of the meta-analysis described below was to investigate the correlation between serum levels of adiponectin (ADPN) and the pathogenesis of hepatocellular carcinoma (HCC). Relevant studies about serum ADPN levels and the pathogenesis of HCC were identified by searching electric databases and by manual search. The included studies were selected in strict accordance with the inclusion and exclusion criteria. Detailed criteria were described in "Materials and methods" section. Statistical analyses were conducted with the STATA 12.0 statistical software (StataCorp, College Station, TX, USA). A total of nine studies were incorporated into this meta-analysis after careful consideration, including 705 HCC patients and 1390 healthy controls. This meta-analysis demonstrated that the serum ADPN levels in HCC patients were significantly higher than those in healthy controls (standard mean difference (SMD) = 0.97, 95% confidence intervals (CI) = 0.02∼1.93, P < 0.05). The result of subgroup analysis by ethnicity revealed that serum ADPN levels in Caucasians and Asians were both obviously higher than those in healthy controls (Caucasians: SMD = 0.51, 95% CI = 0.30∼0.73, P < 0.001; Asians: SMD = 0.49, 95% CI = 0.06∼0.91, P < 0.05), but in Africans, the differences between HCC patients and controls had no statistical significance (SMD = 2.64, 95% CI = -3.01∼8.30, P = 0.36). The evidence obtained by this meta-analysis suggests that serum ADPN levels are associated with the pathogenesis of HCC. Further conclusion might be that increased serum levels of ADPN can inhibit tumor growth and play a protective role in the development of HCC.

EGFR-TKIs added to chemotherapy and EGFR-TKIs single agent have been used as first-line treatment for advanced non-small cell lung cancer patients with and without EGFR mutations. However, direct head-to-head comparison between them is still lacking. We performed indirect comparisons to assess the treatment effects of EGFR-TKIs added to chemotherapy versus EGFR-TKIs alone via common comparator of standard chemotherapy in both subgroups. A comprehensive literature search was undertaken. Finally, 12 randomized controlled trials enrolling more than 2,160 patients with EGFR mutation analysis met the inclusion criteria. We found that EGFR-TKIs combined with chemotherapy did confer an additive PFS advantage over standard chemotherapy both for patients with mutant EGFR tumors (HR 0.54, 95 % CI [0.30, 0.95], P = 0.03) and for patients with wild-type EGFR tumors (HR 0.82, [0.68, 0.98], P = 0.03), but no survival difference between the treatments in both subgroups. When using standard chemotherapy as common comparator, indirect comparison indicated that addition of chemotherapy to EGFR-TKIs did confer an additive PFS benefit (HR 0.38, [0.32, 0.46], P < 0.001) and survival benefit (HR 0.75, [0.66, 0.85], P < 0.001) over EGFR-TKIs alone in patients with wild-type EGFR, but showed a PFS disadvantage (HR 1.35, [1.03, 1.77], P = 0.03) and a marginal trend toward survival disadvantage (HR 1.16, [0.99, 1.35], P = 0.06) compared with EGFR-TKIs alone in patients with mutant EGFR tumors. In summary, addition of chemotherapy to EGFR-TKIs as first-line treatment did confer an additive benefit over EGFR-TKIs alone in patients with wild-type EGFR tumors, but was inferior to EGFR-TKIs alone in patients with mutant EGFR tumors.

MicroRNA (miRNA) played an important role in the progression of liver cancer and its diagnostic and prognostic values have been frequently studied. However, different microarray techniques and small sample size led to inconsistent findings in previous studies. We performed a comprehensive meta-analysis of a total of 357 tumor and 283 noncancerous samples from 12 published miRNA expression studies using robust rank aggregation method. As a result, we identified a statistically significant meta-signature of five upregulated (miR-221, miR-222, miR-93, miR-21 and miR-224) and four downregulated (miR-130a, miR-195, miR-199a and miR-375) miRNAs. We then conducted miRNA target prediction and pathway enrichment analysis to find what biological process these miRNAs might affect. We found that most of the pathways were frequently associated with cell signaling and cancer pathogenesis. Thus these miRNAs may involve in the onset and progression of liver cancer and serve as potential diagnostic and therapeutic targets of this malignancy.

To evaluate the association between BRAF(V) 600E mutation and pathological features in papillary thyroid carcinoma (PTC).

A meta-analysis was performed to estimate the association between HIF-1α polymorphism (C1772T) and breast cancer risk.

To evaluate the relationship between the five common polymorphisms in miRNAs (miR-146a rs2910164 G>C, miR-149 rs2292832 C>T, miR-196a2 rs11614913 C>T, miR-499 rs3746444 A>G and miR-27a rs895819 A>G), and breast cancer (BC) risk.

Gene polymorphisms have been implicated in increased susceptibility of nasopharyngeal carcinoma, but studies have reported inconclusive results. The present study investigates the relationship between each potential gene polymorphism and the risk of nasopharyngeal carcinoma through a comprehensive series of meta-analyses. Data from Pubmed, CNKI, Wanfang and Weipu databases were collected, evaluated and analyzed. Statistical analysis was performed using the Revman 4.2 and STATA 10.0 softwares. A total of 9,705 nasopharyngeal carcinoma cases and 11,041 controls in 34 case-control studies were identified for data analysis. The results suggested that the Arg399Gln polymorphism of XRCC1 gene, the 1G/2G polymorphism of MMP-1 gene, the RsaI polymorphism of CYP2E1 gene, the -1306C>T polymorphism of MMP-2 gene and the Arg72Pro polymorphism of p53 gene might be related to increased risks of nasopharyngeal carcinoma under different genetic comparison models, while the Arg194Trp and Arg280His polymorphisms of XRCC1 gene and the 309T>G polymorphism of MDM2 gene might not contribute to the risk of nasopharyngeal carcinoma. This current meta-analysis suggests that five polymorphisms might be risk factors for nasopharyngeal carcinoma under different genetic comparison models. Future studies are needed to validate our findings.

The process of care for patients with prostate cancer is subject to different degrees of uncertainty. Patients and clinicians could, therefore, greatly benefit from improved prognostic instruments. One emerging tool is the cell cycle progression (CCP) score.

MicroRNAs (miRNAs) are small non-coding RNAs which regulate gene expressions post-transcriptionally. Nowadays, various miRNAs have been found to be sensitive and specific biomarkers for the early diagnosis of colorectal cancer (CRC); however, there are different, even conflicting results in different publications concerning the diagnostic accuracy of miRNA. Therefore, we aim to conduct a meta-analysis of the relevant publications to comprehensively evaluate the diagnostic value of miRNAs in CRC detection. Several public databases such as PubMed, Embase, and Google Scholar were retrieved up to July 13, 2014. Sensitivity was applied to plot the summary receiver operator characteristic (SROC) curve against specificity. The area under the SROC curve (AUC) was calculated to assess the classified effects. STATA 12.0 software was used to perform all statistic analyses. A total of 29 articles, including 80 studies, were involved in our meta-analysis, 55 of which focus on single-miRNA assays and the other 25 on multiple-miRNA assays. Our results suggested that multiple-miRNA assays show a better diagnostic accuracy compared with single-miRNA assays. In addition, blood-based miRNA assays were more accurate than feces-based miRNA assays in CRC diagnosis. Our results also showed that miRNA diagnosis appear to be more accurate in Asians than in Caucasians. However, further researches are needed to validate our results and the feasibility of miRNAs as biomarkers in routine clinical diagnosis of CRC.

Multigene predictors are being used increasingly in early-stage breast cancer patients for prediction and prognosis. However, one consequence of the increased use of multigene predictors, and the heightened efforts toward their incorporation into routine clinical practice, is the potential for future malpractice litigation. It is, therefore, important to ascertain the strength of the evidence for using the different commercially available multigene predictor assays clinically. We evaluated the literature for evidence of clinical validity of four currently available gene signatures and to assess the influence of the 21-gene-expression assay on changes in treatment recommendations.

Nintedanib plus docetaxel has proven an overall survival benefit over docetaxel monotherapy in second-line treatment of non-small-cell lung cancer of adenocarcinoma histology in the LUME-Lung 1 pivotal trial. No published trials have previously compared nintedanib plus docetaxel with agents – other than docetaxel – that are approved second-line treatments for non-small-cell lung cancer.

Genetic polymorphism of miR-34b/c gene is a candidate factor for attributing predisposition to carcinoma. However, results of mounting studies, concerning association of miR-34b/c gene rs4938723 with risk of cancer, present contradictory results. Therefore, a meta-analysis was performed to systematically assessment the possible association between them. The overall results of meta-analysis indicate a significant association was only observed between rs4938723 and cancer risk in genotype model (P(h)=0.203, OR=1.09, 95% CI=1.01-1.70 for CT vs. TT). After stratifying by ethnicity and cancer type, genotype CT of rs4938723 was significantly association with an increased cancer risk in Asian population (P(h)=0.187, OR=1.10, 95%CI=1.01-1.20), allele C and genotype CT were significantly positive associated with hepatocellular cancer (P(h)=0.113, OR=1.11, 95%CI=1.01-1.23 for C vs. T; P(h)=0.121, OR=1.19, 95%CI=1.03-1.37 for CT vs. TT), but rs4938723 was negative associated with risk of colorectal cancer (P(h)=0.342, OR=0.66, 95%CI=0.47-0.92 for CC vs. TT; P(h)=0.519, OR=0.67, 95%CI=0.49-0.93 for CC vs. CT/TT; P(h)=0.443, OR=0.71, 95%CI=0.51-0.99 for CC/TT vs. CT). These findings suggested that rs4938723 was a susceptible locus only for hepatocellular cancer and colorectal cancer.