Reduced DNA repair capacities due to inherited polymorphisms may increase the susceptibility to cancers including gastric cancer. Previous studies investigating the association between Xeroderma Pigmentosum group C (XPC) gene polymorphisms and gastric cancer risk reported inconsistent results. We performed a meta-analysis to summarize the possible association.

quinone oxidoreductase 1 (NQO1) plays a central role in catalyzing the two-electron reduction of quinoid compounds into hydroquinones. The NQO1 Pro187Ser polymorphism was found to correlate with a lower enzymatic activity, which may result in increased incidence of carcinomas including breast cancer. Previous studies investigating the association between NQO1 Pro187Ser polymorphism and breast cancer risk showed inconsistent results. We performed a meta-analysis to summarize the possible association.

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is correlated with a reduced risk of cancer through the reduction of inflammation, which is an important risk factor. Several studies have investigated polymorphisms in the peroxisome proliferator-activated receptor gamma (PPARγ) gene and NSAID use in association with cancer risk. However, these studies yielded mixed results. Therefore, we performed a meta-analysis to evaluate the association of PPARγ polymorphisms and NSAID usage with cancer risk. We conducted a comprehensive search of PubMed through May 2013. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated using the fixed-effect or random-effect model. A comprehensive search of the database revealed 6 studies that fulfilled the inclusion criteria. NSAID use was significantly associated with decreased cancer risk regardless of PPARγ rs1801282 genotypes. In a stratified analysis by cancer type, NSAID users who were minor allele carriers had significantly decreased colon cancer risk compared to non-NSAID users (OR=0.73, 95% CI=0.57-0.93), whereas NSAID users homozygous for the major allele had significantly decreased risk for cancers other than colon cancer compared to non-NSAID users (OR=0.79, 95% CI=0.69-0.91). Our results suggest that the association of PPARγ rs1801282 polymorphism and NSAID use with the risk of cancer may differ according to cancer type.

Dysregulated microRNAs (miRNAs) have been reported to be associated with pancreatic cancer (PaC), suggesting that they may serve as useful novel diagnostic biomarkers for PaC. Various studies have been performed to investigate the diagnostic value of miRNAs for PaC but have obtained conflicting results. Therefore, this meta-analysis aims to comprehensively and quantitatively evaluate the potential diagnostic value of miRNAs for PaC. We systematically searched PubMed, Embase, Google Scholar, Cochrane Library, and Chinese National Knowledge Infrastructure for publications concerning the diagnostic value of miRNAs for PaC without language restriction. The quality of each study was scored using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The summary receiver operator characteristic curve and other parameters were applied to check the overall test performance. Heterogeneity was tested with the I (2) test and publication bias was tested with the Deek's funnel plot asymmetry test. This meta-analysis included 18 articles with a total of 2,036 patients and 1,444 controls. The pooled sensitivity was 82 % (95 % CI, 78-86 %); the specificity was 77 % (95 % CI, 73-81 %); the PLR was 3.6 (95 % CI, 3.0-4.4); the NLR was 0.23 (95 % CI, 0.18-0.29); the DOR was 16 (95 % CI, 10-24); and the AUC was 0.86 (95 % CI, 0.83-0.89). Subgroups analyses were also performed and revealed that there were significant differences between some subgroups: the multiple-miRNAs profiling-based assays, non-blood-based assays, and healthy control-based studies all showed higher accuracies in diagnosing PaC than that of their counterparts. This meta-analysis suggests that the use of miRNAs has potential diagnostic value with a relatively high sensitivity and specificity for PaC, particularly the use of multiple miRNAs for discriminating PaC patients from healthy individuals. More prospective studies on the diagnostic value of miRNAs for PaC are needed in the future.

Molecular biomarkers that can be detected in easily accessible body fluids have been proposed as non-invasive, cost-effective, and useful tools for cancer diagnosis. Recently, extensive research has explored the involvement of the aberrant expression of microRNA-21 (miRNA-21, miR-21) in lung cancer. Inconsistent results, however, have prevented its widespread use in diagnosis. In light of this situation, our meta-analysis aimed to systematically determine whether aberrant miR-21 expression can distinguish patients with lung cancer from cancer-free controls with a high level of diagnostic accuracy. A comprehensive literature search for relevant studies published before December 23, 2013 was conducted in the MEDLINE, EMBASE, the Cochrane Library, and three Chinese databases. The pooled sensitivity, specificity and other parameters were used to assess the overall performance of miR-21-based assays. Statistical analysis was conducted using the STATA 11.0 software. Eleven research articles involving 676 patients with lung cancer and 529 healthy controls were considered eligible for inclusion in the present meta-analysis. The following summary parameters were calculated from all the included studies: sensitivity of 0.66 (95 % confidence interval [CI]: 0.57-0.74), specificity of 0.82 (95 % CI: 0.74-0.88), positive likelihood ratio (PLR) of 3.70 (95 % CI: 2.50-5.60), negative likelihood ratio (NLR) of 0.42 (95 % CI: 0.32-0.54); diagnostic odds ratio (DOR) of 9.00 (95 % CI: 5.00-16.00), and area under the curve (AUC) of 0.81 (95 % CI: 0.77-0.84). In addition, we added two pre-specified covariates (ethnicity and specimen types) to the bivariate model to assess their impact on the diagnostic value of miR-21 for lung cancer. Similar results were also observed in subgroup analyses, indicating a relatively low level of accuracy. The current meta-analysis indicates that a single miR-21 may not be sufficient to identify lung cancer and that more miRNAs should be used to detect lung carcinoma.

Glutathione S-transferase T1 (GSTT1) polymorphic variation has been implicated as a risk factor for various cancers. However, previous studies investigating the association between GSTT1 null genotype and laryngeal cancer risk in Asians reported conflicting outcomes. In the present study, the possible association of laryngeal cancer risk with GSTT1 null genotype was explored by a meta-analysis. Relevant studies were identified through a systemic search of PubMed and Chinese National Knowledge Infrastructure databases. Six studies with a total of 1,824 individuals were included in the meta-analysis. The pooled odds ratio (OR) with 95 % confidence interval (CI) was used to assess the association. Meta-analysis of all included studies showed that there was an obvious association between GSTT1 null genotype and laryngeal cancer risk in Asians (OR = 2.41, 95 % CI 1.27-4.57, P = 0.007, I (2) = 86 %). After adjusting for heterogeneity, there was still an obvious association between GSTT1 null genotype and laryngeal cancer risk in Asians (OR = 1.75, 95 % CI 1.36-2.24, P < 0.001, I (2) = 0 %). The findings from the meta-analysis suggest that GSTT1 null genotype is associated with laryngeal cancer risk in Asians.

To investigate the prognostic and clinicopathological significance of glypican-3 (GPC3) overexpression in hepatocellular carcinoma (HCC).

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR TaqI (rs731236), BsmI (rs1544410) and ApaI (rs7975232) gene polymorphism and the risk of lung cancer using meta-analysis method. The association studies were identified from PubMed and Cochrane Library on 1 December 2013, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR gene polymorphism with lung cancer susceptibility. In the meta-analysis for ApaI gene polymorphism, AA genotype was associated with the risk of lung cancer in Asians. In the meta-analysis for BsmI gene polymorphism, B allele, BB genotype and bb genotype were associated with lung cancer in Asians, and B allele bb genotype were associated with lung cancer risk in overall populations; furthermore, bb genotype was associated with lung cancer risk in Caucasians. In the meta-analysis for TaqI gene polymorphism, t allele and TT genotype were associated with lung cancer in overall populations and in Caucasians. In conclusion, B allele bb genotype t allele and TT genotype were associated with lung cancer risk in overall populations. AA genotype, B allele, BB genotype and bb genotype were associated with the risk of lung cancer in Asians. Furthermore, bb genotype t allele and TT genotype was associated with lung cancer risk in Caucasians. However, more studies should be conducted to confirm it.

Three large-scale genome-wide association studies (GWAS) have identified a shared susceptibility variation phospholipase C epsilon 1 (PLCE1) rs2274223 for esophageal squamous cell carcinoma (ESCC) and/or gastric cardia adenocarcinomas (GCA) in the Chinese population. However, the association between PLCE1 rs2274223 A>G and the risk of digestive tract cancer (DTC) has been inconsistent. We therefore carried out a meta-analysis of published case-control studies to derive a more precise estimation of the association between PLCE1 rs2274223 A>G and DTC risk. A comprehensive search was conducted to identify all eligible studies of PLCE1 rs2274223 polymorphism and DTC risk. Crude odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to estimate the strength of associations in fixed or random effect models. Heterogeneity and publication bias were also assessed. A total of 15 case-control studies were identified, including 29,805 cases and 32,225 controls. Overall, we found a statistically significant association between the PLCE1 rs2274223 polymorphism and DTC risk (G vs A: OR=1.29, 95% CI: 1.17-1.43; GA vs AA: OR=1.33, 95% CI: 1.18-1.51; GG vs AA: OR=1.71, 95% CI: 1.26-2.32; GG/GA vs AA: OR=1.33, 95% CI: 1.17-1.51), but the recessive model did not reach statistical significance (GG vs GA/AA: OR=0.94, 95% CI: 0.63-1.42). In the subgroup analysis by cancer types, we observed a significant risk for DTC in the ESCC and GCA subgroups. When stratified for source of controls, the results of the population-based subgroup analysis showed that the variant G allele might generally induce a significantly increased risk of DTC, except in hospital-based subgroups. In conclusion, PLCE1 rs2274223 polymorphism may be used as a potential biomarker for DTC susceptibility particularly for ESCC and GCA in the Chinese population.

Genetic variation of interleukin-28B (IL-28B) rs12979860 T/C polymorphism is associated with the immune response to interferon (IFN) therapy, which is applied in the treatment of chronic viral hepatitis induced by hepatitis B virus (HBV) and hepatitis C virus (HCV). These chronic liver diseases could progress to end-stage liver diseases, such as hepatocellular carcinoma (HCC). The aim of this study was to clarify whether there exists a causal association between IL-28B rs12979860 T/C polymorphism and development of HCC. In a meta-analysis of six studies with 850 cases and 811 controls, we summarized the data on the association between IL-28B rs12979860 T/C polymorphism and HCC risk and calculated ORs and 95 % CIs to estimate the association strength. We observed that IL-28B rs12979860 T/C polymorphism was positively associated with overall HCC risk (TT vs. CC: OR = 2.38; 95 %, 1.60-3.55; TT vs CT + CC: OR = 1.79; 95 %, 1.23-2.60). In the stratified analysis by ethnicity, the robust association retained in Caucasians with higher risk among TT carriers relative to the CC carriers. A similar trend was found in the studies of healthy controls when data were stratified by source of controls. The combined data suggest that IL-28B rs12979860 T/C polymorphism seems to augment the risk of developing HCC, especially in Caucasians.

Colorectal cancer (CRC) is the worldwide disease which causes enormous losses every year. Recent studies suggested that environmental and gene factors might be the etiologies in increasing the risk of morbidity. Nitric oxide synthase 3 (NOS3) gene polymorphisms are said to be associated with CRC risk but the conclusion is still controversial.

E-Cadherin (CDH1) genetic variations may be involved in invasion and metastasis of various cancers by altering gene transcriptional activity of epithelial cells. However, published studies on the association of CDH1 gene polymorphisms and cancer risk remain contradictory, owing to differences in living habits and genetic backgrounds. To derive a more better and comprehensive conclusion, the present meta-analysis was performed including 57 eligible studies of the association between polymorphisms of CDH1 gene promoter -160 C>A, -347 G>GA and 3'-UTR +54 C>T and cancer risk. Results showed that these three polymorphisms of CDH1 were significantly associated with cancer risk. For -160 C>A polymorphism, -160A allele carriers (CA and CA+AA) had an increased risk of cancer compared with the homozygotes (CC), and the similar result was discovered for the -160A allele in the overall analyses. In the subgroup analyses, obvious elevated risk was found with -160A allele carriers (AA, CA, CA+AA and A allele) for prostate cancer, while a decreased colorectal cancer risk was shown with the AA genotype. For the -347 G>GA polymorphism, the GAGA genotype was associated with increased cancer risk in the overall analysis with homozygous and recessive models. In addition, results of subgroup analysis indicated that the elevated risks were observed in colorectal cancer and Asian descendants. For +54 C>T polymorphism, a decreased risk of cancer was found in heterozygous, dominant and allele models. Moreover, +54T allele carriers (CT, CT+TT genotype and T allele) showed a potential protective factor in gastric cancer and Asian descendants.

Published studies on the association between the Ras Association Domain Family 1 isoform A (RASSF1A) Ala133Ser polymorphism and cancer susceptibility have yielded conflicting results. Thus, a meta- analysis was here performed to assess the possible association.

MicroRNA 200c is a microRNA 200 family member that plays an important role in regulation of the epithelial- to-mesenchymal transition (EMT). The prognostic value of microRNA 200c in solid tumors remains controversial because of inconsistent data. Here, we report a meta-analysis of the association of microRNA 200c expression and survival in patients with solid tumors. Pubmed was searched up to November 2013 for studies investigating microRNA 200c expression and overall survival (OS) in solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) for OS were extracted from each study. Pooled HR and CIs were calculated using the Mantel- Haenszel fixed-effects models. A total of five studies evaluating colorectal cancer, gastric cancer, ovarian cancer, pancreatic cancer and endometrial cancer were included in the analysis. Data were divided into tissue microRNA 200c expression group and serum microRNA 200c expression group. The combined HRs [95%CIs] estimated for OS were 0.62 [0.42-0.91] and 2.16 [1.32-3.52] respectively. Low expression of microRNA 200c in tumor tissue and high expression of microRNA 200c in serum are associated with worse survival in solid tumors. Further study is needed to elucidate this contradiction.

In recent years, numerous studies have been performed to investigate the CCND1 G870A gene polymorphism impact on brain tumors susceptibility. Unfortunately, the results of previous studies were inconsistent. Therefore, we performed a meta-analysis to derive a more precise estimation of any association.

Previous studies have generated conflicting evidence regarding associations between family history and survival after gastric cancer surgery. In this study, we investigated this question using a meta-analysis.

Numerous studies examined the association between excision repair complementation group 1 (ERCC1) expression and the prognosis of gastric cancer patients receiving platinum-based chemotherapy but yielded controversial results. We thus conducted a meta-analysis to quantitatively evaluate the prognostic value of ERCC1 expression in gastric cancer patients receiving platinum-based chemotherapy. A systematic literature search was performed to identify relevant studies in PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and WanFang Database up to December 17, 2013. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (CIs) were estimated. Moreover, meta-regression analysis and subgroup analysis were conducted according to ethnicity, HR extraction, detection methods, survival analysis, and quality score. A total of 1,409 patients from 21 studies were subjected to final analysis. Positive/high ERCC1 expression was significantly associated with poorer overall survival (HR, 1.58; 95 % CI, 1.09-2.28), especially in Asians (HR, 1.81; 95 % CI, 1.20-2.73), and lower response rate (OR, 0.26; 95 % CI, 0.18-0.36), but not with clinicopathological features, such as gender (OR, 1.01; 95 % CI, 0.68-1.51), grade (OR, 0.66; 95 % CI, 0.43-1.01), and stage (OR, 1.05; 95 % CI, 0.58-1.90). This meta-analysis suggested that ERCC1 expression might be a useful biomarker to predict response and survival for gastric cancer patients receiving platinum-based chemotherapy, particularly in Asians.

The CD14-260C/T polymorphism has been implicated to be in association with malignant tumor. However, a number of studies have reported inconclusive results. The aim of this study was to investigate the relationship of CD14-260C/T polymorphism and malignant tumor risk by meta-analysis. A search was performed in PubMed, Embase, the Chinese Journals Full-text Database (CNKI), and Wanfang databases up to August 2013. Odds ratio (OR) and 95 % confidence interval (95 % CI) were used to assess the association. Statistical analysis was calculated by STATA 11.0 software. The polymorphism was identified from 11 articles (12 case-control studies), involving 2,660 cases and 2,943 controls. Overall, no significant association between CD14-260C/T polymorphism and malignant tumor risk was found in the dominant model (TT + TC vs. CC: OR = 0.86, 95 % CI = 0.67-1.11). In the subgroup analysis by malignant tumor types, we found that the heterozygote model (TC vs. CC) might reduce the risk of malignant tumor, especially hematological malignance and prostate cancer (OR = 0.67, 95 % CI = 0.47-0.95), but not associated with gastrointestinal cancer susceptibility. In the subgroup analysis by ethnicity, no significant associations were found among different ethnicities. The study suggested that CD14-260C/T polymorphism might be a protective factor for hematological malignance and prostate tumor susceptibility but not an independent risk factor for gastrointestinal cancer susceptibility. To further evaluate the association between the polymorphism and malignant tumor susceptibility, more studies involving thousands of patients are required.

Molecular characterization of circulating tumor cells (CTCs) found in the blood of cancer patients offers the potential to provide new insights into the biology of cancer metastasis. However, since they are rare and difficult to isolate, the molecular nature of CTCs remains poorly understood. In this paper, we reviewed a decade's worth of scientific literature (2003-2013) describing efforts on isolation and genomic analysis of CTCs. The limited number of CTC genomic studies we found attested to the infancy of this field of study. These initial reports, however, provide an important framework for future comprehensive exploration of CTC biology. For CTCs to be broadly accepted as therapeutic targets and biomarkers of metastatic spread, further in-depth molecular characterization is warranted.

MicroRNA-21 in serum is a promising marker for the diagnosis of lung carcinoma. A meta-analysis was performed to assess the diagnostic accuracy and clinical value of serum microRNA-21 in patients with lung carcinoma.