Glutathione S-transferase M3 (GSTM3) is an important member of the GSTs that plays a critical role in the development of head and neck cancer (HNC). Several studies have investigated between the GSTM3 A/B polymorphism and risk of HNC, however, the results remain controversial. The aim of this meta-analysis is to evaluate the association between the GSTM3 A/B polymorphism and the risk of HNC.

Published data regarding the association between the APE1 Asp148Glu polymorphism and breast cancer susceptibility showed inconclusive results. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. We systematically searched PubMed, Embase, Elsevier, and Springer for relevant articles published before December 10. 2013. The strength of association between APE1 Asp148Glu polymorphism and breast cancer susceptibility was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95% CI) using the software Stata (version 10.0). A total of 7 case-control studies including 3,460 cases and 3,909 controls were included for analysis. Overall, no significant associations were found between the APE1 Asp148Glu polymorphism and breast cancer susceptibility for GG vs TT (OR = 1.00, 95% CI = 0.87-1.14); TG vs TT (OR = 1.06, 95% CI = 0.95-1.18); the dominant model GG + TG vs TT (OR = 1.04, 95% CI = 0.94-1.16) and the recessive model GG vs TG + TT (OR = 0.99, 95% CI = 0.88-1.11). In subgroup analysis, a significant association was found for TG vs TT in Asian subgroup (OR = 1.17, 95% CI = 1.00 ~ 1.36) and in population-based subgroup (OR = 1.18, 95% CI = 1.00 ~ 1.38). This meta-analysis suggested that the APE1 Asp148Glu polymorphism was a risk factor for breast cancer susceptibility among Asian population.

Accumulating evidence has suggested that estrogen receptor alpha (ER-α) PvuII polymorphism might be involved in the development of prostate cancer (PCa). However, the results have been inconsistent. We therefore performed a meta-analysis to clarify the associations between ER-α PvuII polymorphism and PCa. A comprehensive search was conducted to identify all case-control studies of ER-α PvuII polymorphism and PCa risk. We used odds ratios (ORs) to assess the strength of the association and 95% confidence intervals (CIs) to give a sense of the precision of the estimate. A total of 14 studies were found to be eligible for meta-analyses of PvuII variant. Results from this study showed that ER-α PvuII polymorphism were significantly associated with PCa risk under all genetic models in overall population (homogeneous codominant model, OR = 1.57, 95% CI = 1.11-2.21, P = 0.010; heterogeneous codominant model, OR = 1.37, 95% CI = 1.06-1.77, P = 0.02; recessive model, OR = 1.27, 95% CI = 1.02-1.57, P = 0.03; dominant model, OR = 1.40, 95% CI = 1.09-1.79, P = 0.009; and allelic model, OR = 1.25, 95% CI = 1.06-1.48, P = 0.010). Further sensitivity analysis confirmed the significant association. In subgroup analyses stratified by PCa type, there was a significant association between PvuII polymorphism and sporadic PCa risk under both Caucasians and Asians. The meta-analysis indicated elected PvuII polymorphism of ER-α was a risk factor for PCa development.

The Arg188His polymorphism in the XRCC2 gene has been suggested as a risk factor for cancer with inconclusive results. The aim of the current study is to investigate the association between the polymorphism with of cancer by meta-analysis. A total of 33 case-control studies from 27 publications were included for data analyses. The results suggested that the Arg188His polymorphism was not associated with increased/decreased risk of cancer in total analysis (Arg/His+His/His vs. Arg/Arg: OR = 0.98, 95% CI = 0.91-1.06). In the subgroup analysis by ethnicity, no statistical significant association was found in Europeans. In the subgroup analysis by cancer types, statistical significant association was found in ovarian cancer but not in other cancers. The current meta-analysis indicated that the Arg188His polymorphism in the XRCC2 gene might be a risk factor for ovarian cancer. In the future, more large-scale case-control studies are needed to validate our results.

The association between the Arg194Trp polymorphism in the XRCC1 gene and the risk of hematological malignancies has been extensively investigated. However, the results were inconsistent. The objective of the current study is to investigate the association by meta-analysis. We searched the PubMed, Embase, CNKI, Wanfang, and Weipu databases, covering all studies until Aug. 7, 2013. Statistical analysis was performed by using the RevMan4.2 software and the Stata10.0 software. A total of 20 case-control studies concerning the Arg194Trp polymorphism were indentified from 19 articles. In total analysis, our results suggested that the Arg194Trp polymorphism was not associated with an increased/decreased risk of hematological malignancies (odds ratio (OR) = 1.01, 95 % confidence interval (CI) = 0.85-1.22, P = 0.87 for Arg/Trp+Trp/Trp vs. Arg/Arg). In the subgroup analysis by ethnicity, no significant association was found either among Asians (OR = 1.04, 95% CI = 0.84-1.29, P = 0.72) or among Europeans (OR = 1.04, 95% CI = 0.72-1.49, P = 0.83); in the subgroup analyses by cancer types, no significant association was found either among leukemia (OR = 1.10, 95% CI = 0.89-1.35, P = 0.39) or in lymphoma (OR = 0.83, 95% CI = 0.57-1.22, P = 0.35). The current meta-analysis indicated that the Arg194Trp polymorphism in the XRCC1 gene might be not a risk factor for hematological malignancies. In the future, more large-scale case-control studies are needed to validate these results.

Previous epidemiological studies have evaluated the association between common variations of cytochrome P450 (CYP)2C9 (430C>T and 1075A>C) and the risk of colorectal cancer (CRC) with conflicting results. To derive a more precise estimation of the relationship between these CYP2C9 polymorphisms and CRC, a meta-analysis was performed. PubMed, Embase, CNKI, and Web of Science databases were searched. A total of 16 studies including 9,463 cases and 11,416 controls were identified. Potential sources of heterogeneity including ethnicity, sample size of study, genotyping method, diagnostic criteria, and outcome were systematically assessed. Overall, the summary odds ratio of 430T variant for CRC was 0.92 (95% confidence interval (CI) 0.86-0.98; P = 0.012) and 1.39 (95% CI 1.07-1.81; P = 0.013) for colorectal adenomas (CRAs). As for CYP2C9 1075A>C polymorphism, no significant results were observed in overall and subgroup analysis. There was no evidence of publication bias. In conclusion, there is evidence to indicate a significant association between CYP2C9 430C>T polymorphism and CRC/CRA risk.

MicroRNAs (miRNAs) participate in diverse biological pathways and may act as oncogenes or tumor suppressors. Single nucleotide polymorphisms (SNPs) in miRNAs (MirSNPs) might promote carcinogenesis by affecting miRNA function and/or maturation; however, the association between MirSNPs reported and cancer risk remain inconsistent. Here, we investigated the association between nine common MirSNPs and cancer risk using data from large scale case-control studies. Eight precursor-miRNA (pre-miRNA) SNPs (rs2043556/miR-605, rs3746444/miR-499a/b, rs4919510/miR-608, rs2910164/miR-146a, rs11614913/miR-196a2, rs895819/miR-27a, rs2292832/miR-149, rs6505162/miR-423) and one primary-miRNA (pri-miRNA) SNP (rs1834306/miR-100) were analyzed in 16399 cases and 21779 controls from seven published studies in eight common cancers. With a novel statistic, Cross phenotype meta-analysis (CPMA) of the association of MirSNPs with multiple phenotypes indicated rs2910164 C (P = 1.11E-03), rs2043556 C (P = 0.0165), rs6505162 C (P = 2.05E-03) and rs895819 (P = 0.0284) were associated with a significant overall risk of cancer. In conclusion, MirSNPs might affect an individual's susceptibility to various types of cancer.

Whether or not p16 promoter hypermethylation has any prognostic value on the survival of patients with colorectal cancer (CRC) is uncertain. A meta-analysis was therefore conducted on the overall survival involving 16 studies with 3968 patients and disease-free survival involving six studies with 1091 cases, respectively. The promoter hypermethylation was found to be significantly associated with shorter survival compared to controls, which was not only stable according to influence analysis and cumulative meta-analysis but also conclusive according to trial sequential meta-analysis. The meta-analysis supports the hypermethylation as an independent adverse prognostic factor for CRC.

To evaluate the association between the tumour necrosis factor alpha-308 (TNF-α-308) gene polymorphism and the risk of digestive system cancers.

Several studies have examined the associations of polymorphisms in interleukin-6 (IL6) with lung cancer (LC) risk. However, the results were conflicting. Thus, a meta-analysis was conducted to determine the relationship between IL6 polymorphisms and LC risk. Databases including PubMed, EMBASE, Wanfang, and China National Knowledge Infrastructure (CNKI) were searched. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Thirteen studies were included in this meta-analysis. Overall, a significant association between IL6 -634C/G polymorphism and LC susceptibility was observed for GG + CG vs. CC (OR = 1.33, 95% CI 1.20-1.47, P < 0.00001). This polymorphism was also significantly associated with LC risk in Asians (OR = 1.33, 95% CI 1.20-1.47, P < 0.00001), female patients (OR = 1.30, 95% CI 1.11-1.52, P = 0.0009), male patients (OR = 1.25, 95% CI 1.03-1.52, P = 0.02), non-small cell lung cancer patients (OR = 1.21, 95% CI 1.03-1.41, P = 0.02), small cell lung cancer patients (OR = 1.91, 95% CI 1.23-2.97, P = 0.004), smokers (OR = 1.42, 95% CI 1.21-1.65, P < 0.0001), and non-smokers (OR = 1.32, 95% CI 1.13-1.53, P = 0.0003), respectively. No significant result was found for IL6 -174C/G polymorphism. This meta-analysis suggested that IL6 -634C/G polymorphism was a risk factor for LC.

The vitamin D receptor (VDR) can influence cancer susceptibility through binding to vitamin D. However, the previous studies were contradictory. Therefore this meta-analysis was conducted to clarify the association between VDR polymorphisms (BsmI, TaqI, FokI, and ApaI) and cancer risk. One hundred twenty-six studies were enrolled through PubMed. For VDR BsmI polymorphism, significantly increased cancer risks were observed in the overall analysis. In the further stratified analysis, increased risks were observed in colorectal and skin cancer, especially in Caucasian population. However, no significant associations were observed in other VDR polymorphisms in the overall analysis. In the further subgroup analysis, increased risks were found in oral, breast, and basal cell cancer while decreased risk was found in prostate cancer in t allele carriers of TaqI polymorphism. For VDR FokI polymorphism, increased risks were found in ovarian and skin cancer while decreased risk in glioma in f allele carriers. For VDR ApaI polymorphism, increased risk was observed in basal cell cancer, especially in Asian population in a allele carriers. In conclusion, these results indicated that b allele of BamI polymorphism was a risk factor for cancer susceptibility. Meanwhile, t allele of TaqI polymorphism was a risk factor for oral, breast, and basal cell cancer and a protective factor for prostate cancer. Moreover, f allele of FokI polymorphism was a risk factor for ovarian and skin cancer and a protective factor for glioma. Finally, a allele of ApaI polymorphism was a risk factor for basal cell cancer in Asian population.

Many studies were published to assess the association between FASLG T844C polymorphism and susceptibility to breast cancer, but the data were controversial. A meta-analysis was performed to assess the association comprehensively. We performed a comprehensive search in PubMed, Embase, and Web of Science to find eligible studies. Six studies with a total of 6,784 participants were finally included into the meta-analysis. There were a total of 3,382 cases with breast cancer and 3,402 controls in those six studies. Odds ratio (OR) with 95 % confidence interval (95 %CI) was used to evaluate the association. Overall, there was an obvious association between FASLG T844C polymorphism and breast cancer under all four contrast models (for C versus T: OR = 1.26, 95 %CI 1.05-1.50, P OR = 0.011; for CC versus TT: OR = 1.42, 95 %CI 1.11-1.81, P OR = 0.005; for CC versus TT/TC: OR = 1.41, 95 %CI 1.06-1.88, P OR = 0.019; for CC/TC versus TT: OR = 1.16, 95 %CI 1.01-1.33, P OR = 0.038). In the subgroup analysis by ethnicity, there was an obvious association between FASLG T844C polymorphism and breast cancer in Asians, but there was no obvious association in Caucasians. The meta-analysis suggests that there is an association between FASLG T844C polymorphism and susceptibility to breast cancer, especially in Asians.

There are increasing scientific evidences suggesting that E-cadherin gene promoter hypermethylation may contribute to the development and progression of bladder cancer, but existing studies have yielded inconclusive results. This meta-analysis aims to assess the role of E-cadherin promoter hypermethylation in bladder carcinogenesis. We conducted an extensive literature search for relevant studies on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1st, 2013. This meta-analysis was performed using the STATA 12.0 software. Crude risk ratio (RR) with 95% confidence interval (CI) was calculated. Ten clinical studies were included in this meta-analysis with a total of 620 bladder cancer samples,199 normal adjacent samples and 131 normal urothelium tissue. Our meta-analysis revealed that the methylation frequencies in bladder cancer tissues were obviously higher than those in normal control tissues (RR = 2.02, 95%CI: 1.00–4.12, P = 0.050). Subgroup analysis by ethnicity indicated that higher methylation frequencies were observed in bladder cancer tissues among Asian populations (RR = 2.35, 95%CI: 1.11–4.95, P = 0.025), but not among Caucasian populations (RR = 1.62, 95%CI: 0.48–5.53, P = 0.439). Univariate and multivariate meta-regression analyses showed that ethnicity may be the major source of heterogeneity (Pb0.05).No publication bias was detected in this meta-analysis (P=0.358). The present meta-analysis indicates that E-cadherin gene promoter hypermethylation may contribute to increased risk of bladder cancer among Asian populations.

Tumor necrosis factor-alpha (TNF-a) was related to inflammation and involved in the development of colorectal cancer. Polymorphisms located in TNF-a promoter region, such as 308G/A and 238G/A, could affect the risk of various types of cancer by regulating TNF-a production. In this study, a meta-analysis was performed to investigate the association between common polymorphisms of TNF-a promoter region and colorectal cancer susceptibility.

Hepatocellular carcinoma (HCC) is one of the most serious health problems worldwide. As in many other diseases, environment and genetic factors are believed to be involved in the pathogenesis of HCC. Numerous epidemiologic investigations including case-control and cohort studies have suggested the association of glutathione S-transferase (GST) genetic polymorphisms and HCC risk. However, some studies have produced conflicting results. Therefore, we performed an updated meta-analysis to clarify this inconsistency and to establish a comprehensive picture of the association of the polymorphisms of GSTM1 and GSTT1 with HCC susceptibility. We searched PubMed, Embase, ISI Web of Science, and CNKI databases to identify eligible studies meeting the inclusion criteria up to August 30, 2013. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of association. Finally, there were a total of 33 studies with 4,232 cases and 6,601 controls included in this meta-analysis. In the pooled analysis, significantly increased HCC risks were found for null genotype of GSTM1 (OR = 1.31, 95% CI = 1.07-1.61, P = 0.010, P heterogeneity < 10(-5)) and GSTT1 (OR = 1.47, 95% CI = 1.25-1.74, P < 10(-5), P heterogeneity < 10(-5)). Potential sources of heterogeneity were explored by subgroup analysis based on ethnicity, sample size, and source of control. Significant results were found among East Asians and Indians when stratified by ethnicity, while no evidence of significant associations was observed among Caucasian and African populations. In the gene-gene interaction analysis, a statistically significant increased risk for HCC was detected for individuals with combined deletion mutations in both genes compared to those with wild genotypes (OR = 1.88, 95% CI = 1.41-2.50, P < 10(-4), P heterogeneity = 0.004). The present meta-analysis demonstrated that the GSTM1 and GSTT1 null genotype may be associated with an increased risk of HCC and that individuals having the combination of both defective GST genotypes may be more susceptible to developing HCC.

Emerging evidence has shown that single nucleotide polymorphisms occurred in microRNAs may contribute to the development of colorectal cancer (CRC). rs2910164 in miR-146a and rs11614913 in miR-196a2 are suggested to be associated with the susceptibility to CRC, but individually published studies revealed inconclusive results. To systematically summarize the possible correlationship between these polymorphisms and CRC risk, we performed this meta-analysis.

LGALS3 plays a role in colorectal cancer, however, the detailed molecular mechanism remains to be determined, while signaling pathways provide valuable information for understanding the underlying mechanism of the cancer. The purpose of this study was to explore the roles of LGALS3 and signaling pathways in the pathogenesis of colorectal cancer. In this study, microarray data GSE8671 were downloaded from the Gene Expression Omnibus database and differentially expressed genes (DEGs) in colorectal cancer were identified by Significant Analysis of Microarray. Gene ontology (GO) analysis was performed on the top 500 upregulated and 500 downregulated genes using DAVID. The signaling pathways were predicted by the signaling pathway impact analysis (SPIA) with pGFdr<0.05 and transcription factors were identified by TFats. The LGALS3-related protein-protein interaction network (PPI) was established by STRING and Cytoscape. In total, 6,593 upregulated and 5,897 downregulated DEGs were identified and 41 downregulated genes, including CLND8 and CLND23 were enriched in cell adhesion. In addition, 21 pathways, such as the cell cycle, p53 signaling pathway and NF-κB signaling pathway, were selected. MYC and TCF7L2 were found to be activated while FOXO3 was suppressed in colorectal cancer. Eight downregulated and 10 upregulated genes were identified in the LGALS3 PPI network. Results of the present study shed new light on the molecular mechanism of colorectal cancer and these findings have the potential to be used in colorectal cancer treatment.

The cell cycle is a conserved process from yeast to mammals and focuses on mechanisms that regulate the timing and frequency of DNA replication and cell division. The temporal and spatial expression of the genes is tightly regulated to ensure accurate replication and transmission of DNA to daughter cells during the cycle. Although the genes involved in interphase are well studied, most of the genes which are involved in mitotic events still remain unidentified. Since, the discovery of mitosis related genes is still incomplete, we performed a co-expression and gene ontology analysis for revealing novel mitosis regulated genes. In this study, we showed that C12orf48 is co-expressed with well-known mitotic genes. Moreover, it is also co-expressed with the genes that have roles in interphase such as DNA replication. Furthermore, our results showed that C12orf48 is also differentially expressed in various cancers. Therefore, the results presented in this study suggest that C12orf48 may be an important molecule for both interphase and mitosis. Since, the molecules involved in these mechanisms are crucial for proliferation as well as in carcinogenesis, C12orf48 should be considered as a novel cell cycle and carcinogenesis related gene.

Cytochrome P450 1A1 (CYP1A1) is a member of the CYP1 family, which is a key enzyme in the metabolism of many endogenous substrates and exogenous carcinogens. To date, many studies have examined the association between CYP1A1 MspI and Ile462Val polymorphisms and cancer risk in various populations, but their results have been conflicting rather than consistent.

Human papillomavirus (HPV) infection is considered the major cause of cervical cancer (CC), but a number of infected women do not develop invasive lesions, suggesting the role of genetic susceptibility and environmental co-factors for cancer outbreak. Glutathione S- transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens.