The associations between IL-6 gene single nucleotide polymorphisms (SNPs) and risk of hepatocellular carcinoma (HCC) are controversial. We performed a meta-analysis to provide more credible evidence. We searched for relevant studies published up to 2013 by performing an efficient searching strategy. Odds ratios (OR) with 95% confidence interval (95% CI) was used to estimate the strength of the associations between IL-6 polymorphisms and HCC risk. We identified eight case-control studies involving 1,448 HCC cases and 3,160 controls. Our estimation specifically focused on two SNPs of the IL-6 gene, -174 G/C and -572 G/C. The combined results showed that association between IL-6-174 G/C polymorphism and risk of HCC was significant under additive model (CC vs. GG: OR 0.36; 95% CI, 0.16, 0.85) and recessive model (GG+CG vs. CC: OR 2.82; 95% CI 1.26, 6.28). However, the IL-6-572 G/C polymorphism was not associated with HCC risk. In conclusion, IL-6-174 G/C, but not -572 G/C polymorphism could be a candidate for susceptibility to HCC. However, the results should be cautiously interpreted due to the limited number of the included studies.

Vitamin D plays a central role in cellular proliferation, apoptosis induction, and tumor growth suppression. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D. A series of epidemiological studies have examined the association between the VDR FokI polymorphism and breast cancer risk, but the findings remain inconclusive. Fifteen eligible case-control studies involving 15,681 cancer cases and 20,632 control subjects were identified through searching PubMed, Embase, and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association. Heterogeneity across studies was examined with the chi-square-based Q test and the I (2) index. Begg's and Egger's test were also performed to determine publication bias. All statistical data were analyzed by STATA software. The combined estimates did not show significant risks correlated with the FokI polymorphism. However, we found an increased risk in the subgroup analysis by source of control (OR = 1.11, 95% CI = 1.01-1.22; heterogeneity test: P = 0.116, I(2) = 0.0% for ff vs FF; OR = 1.10, 95% CI = 1.01-1.21; heterogeneity test: P = 0.832, I(2) = 0.0% for ff vs Ff + FF). This meta-analysis suggests that the presence of FokI polymorphism may contribute to the risk of breast cancer in Caucasians.

Previous studies have suggested that the glutathione S-transferases M1 (GSTM1) null genotype is associated with the risk of gastric cancer. However, the interaction between GSTM1 null genotype and smoking for the risk of gastric cancer is still elusive. Therefore, we performed a meta-analysis to ascertain this issue. Databases of PubMed, EMBASE, and China National Knowledge Infrastructure were searched to retrieve relevant studies. Smokers were categorized as "ever-smokers" and "non-smokers." Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to estimate the association strength. Subgroup analyses according to ethnicity, source of control, and sample size were also conducted. A total of 15 eligible studies, including 4,687 gastric cancer cases and 7,002 controls, were identified. We found that the GSTM1 null genotype was associated with increased risk of gastric cancer among ever-smokers (OR = 1.460, 95% CI 1.064-2.003, heterogeneity: P = 0.019). The null genotype also significantly increased the risk of gastric cancer among non-smokers (OR = 1.777, 95% CI 1.301-2.426, heterogeneity: P < 0.01). Stratified analysis according to ethnicity showed that the GSTM1 null genotype was associated with increased risk of gastric cancer among Asians both in ever-smokers (OR = 1.841, 95% CI 1.184-2.861) and non-smokers (OR = 1.773, 95% CI 1.382-2.275). In conclusion, the GSMT1 null genotype significantly increased the risk of gastric cancer both in ever-smokers and non-smokers.

In this paper, we provide a comprehensive summary of available clear cell renal cell carcinoma (ccRCC) microarray data in the form of meta-analysis of genes differentially regulated in tumors as compared to healthy tissue, using effect size to measure the strength of a relationship between the disease and gene expression. We identified 725 differentially regulated genes, with a number of interesting targets, such as TMEM213, SMIM5, or ATPases: ATP6V0A4 and ATP6V1G3, of which limited or no information is available in terms of their function in ccRCC pathology. Downregulated genes tended to represent pathways related to tissue remodeling, blood clotting, vasodilation, and energy metabolism, while upregulated genes were classified into pathways generally deregulated in cancers: immune system response, inflammatory response, angiogenesis, and apoptosis. One hundred fifteen deregulated genes were included in network analysis, with EGLN3, AP-2, NR3C1, HIF1A, and EPAS1 (gene encoding HIF2-α) as points of functional convergence, but, interestingly, 610 genes failed to join previously identified molecular networks. Furthermore, we validated the expression of 14 top deregulated genes in independent sample set of 32 ccRCC tumors by qPCR and tested if it could serve as a marker of disease progression. We found a correlation of high fucosyltransferase 11 (FUT11) expression with non-symptomatic course of the disease, which suggests that FUT11's expression might be potentially used as a biomarker of disease progression.

Interleukin-4 (IL-4) -524C > T polymorphism has been implicated to alter the risk of colorectal cancer (CRC), but the results are controversial. The objective of this study was to quantitatively evaluate the association between IL-4 -524C > T polymorphism and CRC risk. A comprehensive search was conducted to identify all eligible studies of IL-4 -524C > T polymorphism and CRC risk. Statistical analysis was performed with Review Manager 5.0 and Stata 11. A total of 5 case-control studies, including 1,224 cases and 1,551 controls, were included. The combined results based on all eligible studies suggested that IL-4 -524C > T polymorphism was not associated with CRC susceptibility. When stratifying for race, the data showed that the IL-4 -524C > T polymorphism was also not associated with an increased CRC susceptibility in Caucasians. Our study suggests that IL-4 -524C > T polymorphism may be not associated with an increased CRC susceptibility.

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene polymorphisms have been associated with many autoimmune diseases and malignancy susceptibility, but the relationship between CTLA-4 and cervical cancer is still controversial. Hence, a meta-analysis of the published studies for the CTLA-4 gene polymorphisms and the risk of cervical cancer was performed to evaluate the association between them. Odds ratios (ORs) and 95% confidence intervals (CIs) for the codominant, dominant, and recessive genetic models were assessed. The fixed or random effect pooled measure was selected on the basis of the heterogeneity test among studies. The heterogeneity among studies was evaluated using the I (2). Eight studies with 2,835 cases and 2,560 controls were included. In seven studies for the CTLA-4 +49A/G polymorphism, a significant association was showed between the A allele and the increased risk of cervical cancer in the codominant (OR 1.16, 95% CI 1.05-1.29), dominant (OR 1.18, 95% CI 1.03-1.36), and recessive (OR 1.24, 95% CI 1.05-1.56) models. In five studies for the CTLA-4 -318C/T polymorphism, the meta-analysis showed a significant association of the C allele with the reduced risk of cervical cancer in the codominant (OR 0.79, 95% CI 0.66-0.94) and recessive (OR 0.76, 95% CI 0.63-0.93) models. This meta-analysis suggested that +49A/G and -318C/T polymorphisms of the CTLA-4 gene were significantly associated with the risk of cervical cancer. However, further studies are required to draw a solid conclusion on the relation between the CTLA-4 polymorphism and the risk of cervical cancer.

Several studies have indicated an association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and the risk of hepatocellular carcinoma (HCC). However, the conclusions are inconsistent. Therefore, a meta-analysis was performed.

X-ray repair cross-complementing group 3 (XRCC3) is responsible for maintaining the integrity of the genome, playing a critical role in protecting it against mutations which lead to cancer. Polymorphisms at exons 7 of the XRCC3 gene may alter the XRCC3 repair efficiency. The aim of this study is to derive a precise estimation of the relationship between XRCC3 Thr241Met polymorphism and gastric cancer (GC) risk.

MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs). Single nucleotide polymorphisms (SNPs) in miRNAs may contribute to cancer susceptibility due to changes in the microRNA's properties and/or maturation. The present study aimed to investigate the association between two miRNA polymorphisms (miR-499 rs3746444 and miR-149 rs2292832) and gastrointestinal (GI) cancer risk.

Glioma is rarely curable, and factors that influence the prognosis of glioma patients are not fully understood. Loss of heterozygosity (LOH) of 1p/19q has long been known to be a typical molecular signature of oligodendroglial neoplasms. However, whether LOH of 1p/19q is associated with survival in gliomas remains controversial. Here our goal was to evaluate the association between LOH of 1p/19q and progression-free survival (PFS) and overall survival (OS) by conducting a meta-analysis among glioma cases.

Insulin-like growth factor 1 (IGF1)(CA)19 and insulin-like growth factor-binding protein-3 (IGFBP-3)-202A/C gene polymorphisms had been focused by many epidemiological studies recently, which were associated with common cancer risk including colorectal, breast, prostate, and lung cancer. However, the findings of epidemiological investigations are not coincident. We did a systematic review and meta-analysis of case-control studies, including studies nested in cohorts, of the association between IGF1(CA)19 and IGFBP-3-202A/C gene polymorphism and prostate, colorectal, premenopausal and postmenopausal breast cancer. We identified 17 eligible studies (24 datasets), which included 9,744 cases and 11,332 controls. The result displays that individuals carrying (CA)19 allele had a subtly decreased risk of all cancer sites [OR(95% CI) 0.92(0.87,0.97); 0.882(0.809,0.962); 0.902(0.849,0.958)] and postmenopausal breast cancer [OR(95% CI) 0.893(0.832,0.959); 0.834(0.719,0.968); 0.862(0.776,0.958)] in allele contrast model, CA19/CA19 vs. non-CA19/non-CA19 model, and recessive genetic model. In subgroup analysis according to ethnicities, (CA)19 repeat polymorphism had an increased risk of common cancers in Asian [OR (95% CI) of allele contrast model: 1.105(1.000,1.224); additive model: 1.103(0.844,1.441), 1.197(1.013,1.413); recessive model: 1.039(0.831,1.300); and dominant model: 1.191(1.030,1.376)]. On the other hand, IGFBP-3-202A/C gene polymorphism did not seem to be associated with all the cancer sites in any genetic model and ethnicity. In conclusion, the result of this meta-analysis indicates that the IGF1(CA)19 polymorphism is a candidate gene polymorphism for cancer susceptibility regardless of environmental factors, especially in Asian.

Many studies have examined the association between APE1 Asp148Glu (rs3136820) polymorphism gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. PubMed and CNKI databases were searched for case-control studies published up to October 2013. Data were extracted, and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 14 studies, comprising 4,165 lung cancer cases and 5,438 controls were included. Overall, for Glu carriers (Asp/Glu + Glu/Glu) versus wild-type homozygotes (Asp/Asp), the pooled OR was 1.05 (95% CI = 0.96-1.15 P = 0.000 for heterogeneity); for Glu/Glu versus Asp/Asp, the pooled OR was 1.07 (95% CI = 0.95-1.21 P = 0.007 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were not found among Asians or Caucasians. This updated meta-analysis suggests that the APE1 Asp148Glu polymorphisms are not associated with lung cancer risk among Asians or Caucasians.

Cytotoxic T lymphocyte antigen-4 (CTLA-4), a key gene that contributes to the susceptibility and clinical course of cancer, is an important down-regulator of T cell activation and proliferation. The +49A/G polymorphism is commonly studied because of its association with cancer risks. However, other polymorphisms, such as -1722T/C and -1661A/G, have not been studied in detail. We performed a meta-analysis using 43 eligible case-control studies with a total of 19,089 patients and 21,388 controls to examine the association between CTLA-4 +49A/G, -1722T/C, and -1661A/G polymorphisms and cancer risk. We searched the PubMed and EMBASE databases for all articles published up to July 17, 2013. Individuals with the +49 A allele (AA/AG vs. GG, odds ratio (OR) = 1.21, 95% confidence interval (95% CI) = 1.16-1.27) and -1661 G allele (AG/GG vs. AA, OR = 1.52, 95% CI = 1.34-1.73) had increased cancer risk. However, no significant association between cancer risk and the -1722T/C polymorphism was found (CC/CT vs. TT, OR = 1.04, 95% CI = 0.92-1.16). In subgroup analysis for the +49A/G polymorphism, increased cancer risk remained in the subgroups of Asians (OR = 1.25, 95 % CI = 1.18-1.31), patients with breast cancer (OR = 1.28, 95% CI = 1.15-1.42), and patients with lung cancer (OR = 1.20, 95 % CI = 1.07-1.35). For the -1661A/G polymorphism, increased cancer risk remained in the subgroups of Asians (OR = 1.52, 95% CI = 1.34-1.73), patients with breast cancer (OR = 1.48, 95% CI = 1.07-2.03), and patients with oral cancer (OR = 3.16, 95% CI = 1.84-5.45). However, no significant increase in cancer risk was found in the subgroups for the -1722T/C polymorphism. In conclusion, the results suggest that +49A/G and -1661A/G polymorphisms in CTLA-4 are risk factors for cancers, whereas the -1722T/C polymorphism is not associated with an increased risk of cancer.

A2455G is a common polymorphism in CYP1A1, showing differences in its biological functions. Case-control studies have been performed to elucidate the role of A2455G in cancer; however, the results are conflicting and heterogeneous. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and A2455G (64,593 cases and 91,056 controls from 272 studies) polymorphism in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model, odds ration [OR] = 1.19, 95% confidence interval [CI] = 1.13-1.25; recessive model: OR = 1.41, 95% CI = 1.29-1.54; additive model: OR = 1.49, 95% CI = 1.35-1.65) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of breast cancer, colorectal cancer, esophageal cancer, hepatocellular cancer, head and neck cancer, leukemia, lung cancer, and prostate cancer, but these associations vary in different ethnic populations. In summary, this meta-analysis suggests the participation of A2455G in the susceptibility for some cancers, such as breast cancer, colorectal cancer, lung cancer, and so on. Moreover, ethnicity, histological type of cancer, and smokers seem to contribute to varying expressions of the A2455G on some cancers risk. In addition, our work also points out the importance of new studies for A2455G polymorphism in some cancer types, such as gallbladder cancer, Indians of breast cancer, and Caucasians of ovarians, because these cancer types had high heterogeneity in this meta-analysis (I(2) > 75%).

The Val158Met polymorphism in the COMT gene may affect the DNA repair pathways and be associated with the risk of cancer in Chinese population. However, the results of previous studies are inconsistent. The objective of this study was to investigate the association between the Val158Met polymorphism in the COMT gene and the risk of cancer for Chinese population by meta-analysis. We searched PubMed, Embase, CNKI, Weipu, and Wanfang databases, and the last search was updated on Sep. 26, 2013. Statistical analysis was performed using the Revman4.2 and Stata10.0 software. A total of 18 case-control studies concerning 5034 case and 6234 controls were included. In the total analysis, the results suggested a significant association between the Val158Met polymorphism in the COMT gene and the cancer risk in Chinese population: OR = 1.34, 95%CI = 1.04-1.73, and P = 0.03 for AA vs. AG + GG; OR = 1.39, 95%CI = 1.06-1.82, and P = 0.02; OR = 1.13, 95%CI = 1.01-1.27, and P = 0.04. In the subgroup analysis by cancer types, significant association was found in the breast cancer and esophageal squamous cell carcinoma. The current meta-analysis confirmed that the Val158Met polymorphism in the COMT gene may be a risk factor for cancer in Chinese population. In the future, more case-control studies are needed to validate our results.

The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met (rs861539) polymorphism and the risk of leukemia remains inclusive or controversial. For a better understanding of the effect of XRCC3 Thr241Met (rs861539) polymorphism on leukemia risk, we performed a meta-analysis. All eligible studies were identified through a search of PubMed, Excerpta Medica Database (Embase) and the Chinese Biomedical Literature Database (CBM) up to August 2013. The association between the XRCC3 Thr241Met (rs861539) polymorphism and leukemia risk was analyzed by means of odds ratios (ORs) and 95% confidence intervals (CI). Ultimately, seven studies with 1070 cases and 1850 controls were included in the meta-analysis. There was no association between Thr241Met polymorphism and leukemia risk in any of the five models in the overall populations (T vs. C: OR = 1.43, 95% CI = 0.95-2.13, p = 0.086; TT vs. CC: OR = 1.71, 95% CI = 0.88-3.33, p = 0.112; TC vs. CC: OR = 1.35, 95% CI = 0.96-1.91, p = 0.089; TT vs.

We propose and discuss a method for doing gene expression meta-analysis (multiple datasets) across multiplex measurement modalities measuring the expression of many genes simultaneously (e.g. microarrays and RNAseq) using external control samples and a method of heterogeneity detection to identify and filter on comparable gene expression measurements. We demonstrate this approach on publicly available gene expression datasets from samples of medulloblastoma and normal cerebellar tissue and identify some potential new targets in the treatment of medulloblastoma.

Human oxoguanine glycosylase 1 (hOGG1) is an important part in the base excision repair (BER) pathway of DNA repair. Numerous epidemiological studies were published to assess the association between hOGG1 C8069G polymorphism and risk of colorectal cancer, but they reported contradictory results. A meta-analysis was performed to clarify the effect of hOGG1 C8069G polymorphism on colorectal cancer. The association was assessed by calculating the pooled odds ratio (OR) with 95% confidence interval (95 %CI). Twenty-one studies with a total of 14,492 participants were finally included into the meta-analysis. Overall, there was an obvious association between hOGG1 C8069G polymorphism and increased risk of colorectal cancer under all four genetic models (G vs. C: OR = 1.17, 95%CI 1.05-1.30, P = 0.003; GG vs. CC: OR = 1.39, 95%CI 1.11-1.74, P = 0.004; GG/CG vs. CC: OR = 1.20, 95%CI 1.04-1.37, P = 0.010; GG vs.

Case-control studies on the association between mouse double minute 2 homolog (MDM2) rs2279744 polymorphism and endometrial cancer have provided either controversial or inconclusive results. To clarify the effect of MDM2 rs2279744 polymorphism on the risk of endometrial cancer, a meta-analysis of all case-control observational studies was performed. Pooled odds ratios (ORs) for various polymorphisms were estimated using random and fixed effect models. Q-statistic was used to evaluate the homogeneity, and Egger and Begg tests were used to assess publication bias. Overall, the MDM2 rs2279744 polymorphism was associated with a risk of endometrial cancer (OR = 0.76; 95% CI = 0.64-0.90 for allele contrast, p = 0.002, P(het) = 0.003). The contrast of homozygotes and the recessive and dominant models produced the same pattern of results as the allele contrast. In the analysis stratified by ethnicity, significant associations were found in the Caucasian population in all of the genetic models. Our pooled data suggest evidence for a major role of MDM2 rs2279744 polymorphism in the carcinogenesis of endometrial cancer, especially among Caucasian populations.

Hypoxia-inducible factor-1 (HIF-1) influences cancer progression and metastasis through various mechanisms, and HIF-1α polymorphisms are reportedly associated with many cancers; however, the associations of HIF-1α P582S and A588T polymorphisms with the risk of digestive system cancer remain inconclusive. To understand the role of HIF-1α P582S and A588T genotypes in digestive cancer development, we conducted a comprehensive meta-analysis involving 1,517 cases and 3,740 controls. Overall, the P582S polymorphism was not significantly associated with digestive system cancers in all genotypes. By contrast, the A588T polymorphism was significantly associated with digestive system cancers in the dominant model (TT/AT vs. AA: OR = 3.17, 95% CI: 1.21, 8.25; P heterogeneity < 0.001). In subgroup analysis for cancer types, the two polymorphisms were only associated with increased risk of pancreatic cancer (P582S: SS vs. PP: OR = 2.51, 95% CI: 1.31, 4.81; SS vs.