Genetic polymorphisms of cyclooxygenase-2 (Cox-2) gene have been implicated in the susceptibility to hepatocellular carcinoma (HCC), but the findings from published studies are conflicting and inconclusive. To obtain a more precise estimate of the association of Cox-2 polymorphisms with HCC risk, we performed a meta-analysis of eight eligible case-control studies identified through an extensive online database search of PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang and Chinese Biomedicine Database; after exclusion, 2324 cases and 2604 controls were included. The pooled odds ratios with corresponding 95% confidence intervals were calculated to assess associations, using fixed- or random-effect models. In addition, subgroup analysis by ethnicity and sensitivity analysis were performed. Our results showed that the Cox-2 rs20417 (-765 G/C) polymorphism was not associated with HCC risk in the studied genetic contrast modes (C vs. G, GC vs. GG, and CC + GC vs. GG). No significant association was found with ethnic groups examined (P > 0.05). Similarly, no significant association of the Cox-2 rs5275 (+ 8473 T/C) polymorphism and HCC risk was found under any of the studied contrasts (C vs. T, TC vs. TT, CC vs. TT, CC + TC vs. TT, CC vs. TC + TT). The present meta-analysis, combining all currently available data, suggests no significant associations of either Cox-2 polymorphism with HCC risk. Further studies with a larger sample size are needed to determine the association in different ethnicities.

Previous studies examining the association between p73 G4A and gastric cancer risk have produced inconsistent results. The objective of this study was to clarify whether p73 G4A plays a major role in the development of gastric cancer. Studies that had examined the association between p73 G4A and gastric cancer risk were identified through PubMed, Science Direct, and CNKI. We selected eligible studies based on inclusion criteria. Odds ratios were estimated using distinct genetic models, and the heterogeneity between studies was explored using Cochran's Q statistic along with the I(2) statistic. Overall, we found no evidence of a significant association between p73 G4A and risk of gastric cancer. A same trend was also indicated in subgroup analysis by ethnicity. The heterogeneity tests revealed that there was no significant heterogeneity across studies. Our meta-analysis indicates that p73 G4A might not have a major effect on risk of gastric cancer. A much larger study is required to validate our findings.

Tumor suppressor gene p53 functions as the guardian of the human genome and mutations in p53 contribute to cancer development. However, studies that investigated the potential of p53 as a prognostic marker in osteosarcoma patients have yielded inconclusive results. Based on recommendation of the Cochrane Collaboration, this meta-analysis was conducted using data from the 17 published studies to evaluate the association of p53 alterations with clinical outcome of osteosarcoma patients. Different databases, including MEDLINE, PsycINFO, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Prognostic value of p53 alterations was determined by risk ratio (RR). The data showed that p53-positive immunostaining tended to associate with decreased 2-year survival rates (RR, 1.94; 95% CI, 1.43 to 2.64; p < 0.0001, I(2) = 10%). However, the prediction value of RR was smaller with p53 expression than with p53 mutations. Moreover, patients who received neoadjuvant chemotherapy and surgery tended to have a stronger association between p53-positive staining and 2-year mortality compared to the patients treated with surgery only. However, p53-positive staining was not associated with 3-year (RR, 1.64; 95% CI, 0.84 to 3.20; P = 0.15; I(2) = 56%) and 5-year survival (RR, 1.25; 95% CI, 0.78 to 2.01; P = 0.36; I(2) = 70%). The data from the current study suggest that p53-positive osteosarcoma only predicted a decreased short-term survival rate, but not 3- or 5-year survival.

rs895819 and rs11671784 are 2 SNPs in miR-27a that can influence the expression of mature miRNA. However, their role in gastric cancer development is still not well understood. This study aimed to determine whether these 2 polymorphisms are associated with gastric cancer risk in a Chinese population and how they influence the expression of miR-27a.

Cyclin D1 polymorphism has been reported to be associated with risk of breast cancer, but the published studies have yielded controversial results. This study was undertaken to derive a precise risk estimate for the cyclin D1 polymorphism associated with breast cancer risk. We performed a search of EMBASE, PubMed, and Web of Science. In total, data from 18 publications were pooled and the association was assessed by odds ratios (ORs) with 95 % confidence intervals (CIs). This analysis showed that there was no obvious association between the cyclin D1 polymorphism and breast cancer risk in any of the analyzed genetic model. We found the same negative association in stratified analyses by ethnicity, source of controls, and sample size. Our meta-analysis provides an estimate that the presence of cyclin D1 polymorphism may not confer susceptibility to breast cancer.

Gender-based differences in disease onset in murine models of malignant peripheral nerve sheath tumor (MPNST) and in patients with Neurofibromatosis type-1-(NF-1)-associated or spontaneous MPNST has not been well studied.

Growing evidences show that matrix metalloproteinase 1 (MMP1) plays important roles in tumorigenesis and cancer metastasis. MMP1 -1607 1G>2G is a single nucleotide polymorphism in the promoter region of MMP1 and affects MMP1 production. Analysis of previous studies on the association of -1607 1G>2G polymorphism with different cancer types remained to be illustrated. To further assess the effect of -1607 1G>2G polymorphism on cancer risk, we performed this meta-analyses, up to September 8, 2014, of 10,640 cases and 10,915 controls from 42 published case-control designed studies. Statistical analyses were performed using STATA 11.0 software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. ORs with 95% CIs for the polymorphism MMP1 -1607 1G>2G and cancer were estimated using fixed and random effects models when appropriate. Significantly increased risks were found in overall under the models of 2G vs.1G, 2G2G vs. 1G1G, 2G2G/1G2G vs. 1G1G, and 2G2G vs. 2G1G/1G1G. Significantly elevated risks were observed in colorectal adenoma under the models of 2G vs. 1G, 2G2G vs. 1G1G, 2G2G/1G2G vs. 1G1G, and 2G2G vs. 2G1G/1G1G and lung cancer and head and neck cancer under the models of 2G vs. 1G. We found that significantly elevated risks were observed in Asian population and hospital-based studies in most comparison models tested. Thus, this meta-analysis indicates that the polymorphism MMP1 -1607 1G>2G is significantly associated with a significantly increased risk of cancers and may provide evidence-based medical certificate to study the cancer susceptibility.

Bevacizumab (Bev) combined with chemotherapy significantly improves progression-free survival (PFS) but not overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The efficacy and safety depend on the type of chemotherapy combined with Bev. We performed a meta-analysis of phase III trials to evaluate the efficacy and safety of Bev + standard chemotherapy for HER2-negative MBC. The Cochrane Central Register of Controlled Trials, the Cochrane databases, EMBASE, MEDLINE, and ClinicalTrials.gov were analyzed. The primary outcomes included PFS, OS, and toxicity. Event-based hazard ratios (HRs) and relative risks (RRs) were expressed with the 95% confidence intervals (CIs). Four randomized controlled trials consisting of 3082 patients were included. Bev + standard chemotherapy improved PFS (HR 0.70, CI 0.64-0.77, P = 0.000) but had no effect on OS (HR 0.92, CI 0.82-1.02, P = 0.119). Bev + chemotherapy increased the incidence of febrile neutropenia (RR 1.45, CI 1.00 to 2.09, P = 0.048), proteinuria (RR 11.68, CI 3.72-36.70, P = 0.000), sensory neuropathy (RR 1.33, CI 1.05-1.70, P = 0.020), and grade ≥3 hypertension (RR 13.94, CI 7.06-27.55, P = 0.000). No differences in efficacy were observed between Bev + paclitaxel and Bev + capecitabine (Cape), but Bev + Cape increased the incidence of neutropenia. Bev + standard chemotherapy improved PFS in HER2-negative MBC patients. No benefit in OS was observed. Bev + Cape and Bev + paclitaxel had similar treatment efficacy, but Bev + Cape had a higher incidence of neutropenia.

To systematically evaluate the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer.

Connexins and their cell membrane channels contribute to the control of cell proliferation and compartmental functions in breast glands and their deregulation is linked to breast carcinogenesis. Our aim was to correlate connexin expression with tumor progression and prognosis in primary breast cancers.

Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulin. In addition to genetic changes, gene hypermethylation is an alternative mechanism of tumor suppressor gene inactivation in MM. The cyclin-dependent kinase inhibitor 1 (CDKN2B or p15(INK4B) ) gene lies adjacent to the tumor suppressor gene, cyclin-dependent kinase inhibitor 2 (CDKN2A), and is frequently mutated and deleted in a wide variety of tumors, including MM. However, there is a lack of systematic analysis of p15 epigenetic modification such as methylation in MM from different studies that can provide more powerful estimation of an effect. In this study, we have systematically reviewed the studies of p15(INK4B) promoter methylation in MM and quantified the association between p15(INK4B) promoter methylation and MM using meta-analysis methods. We observed that the frequency of p15(INK4B) methylation is significantly higher in MM patients than in normal healthy controls. The pooled odds ratio (OR) from ten studies including 394 MM and 99 normal individuals is 0.08, while confidence interval (CI) is 0.03-0.21 (P<0.00001). This indicates that p15(INK4B) inactivation through methylation plays an important role in the pathogenesis of MM. In addition, the frequency of p15(INK4B) methylation was significantly higher in patients with MM than in those with asymptomatic monoclonal gammopathy of undetermined significance. The pooled OR from four studies is 0.40, 95% CI =0.21-0.78 (P=0.007). These results suggest that silencing of p15(INK4B) gene expression by epigenetic modification such as promoter hypermethylation plays a role not only in the initiation of MM but also in plasma cell malignant transformation, disease progression, and development.

There is growing evidence that the ghrelin axis, including ghrelin (GHRL) and its receptor, the growth hormone secretagogue receptor (GHSR), play a role in cancer progression. Ghrelin gene and ghrelin receptor gene polymorphisms have been reported to have a range of effects in cancer, from increased risk, to protection from cancer, or having no association. In this study we aimed to clarify the role of ghrelin and ghrelin receptor polymorphisms in cancer by performing a meta-analysis of published case-control studies.

MicroRNA-21 (miR-21) has been suggested to play a significant role in the prognosis of carcinoma. The recognition of novel biomarkers for the prediction of cancer outcomes is urgently required. However, the potential prognostic value of miR-21 in various types of human malignancy remains controversial. The present meta-analysis summarises and analyses the associations between miR-21 status and overall survival (OS) in a variety of tumours.

Three extensively investigated polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) in the X-ray repair cross-complementing group 1 (XRCC1) gene have been implicated in risk for glioma. However, the results from different studies remain inconsistent. To clarify these conflicts, we performed a quantitative synthesis of the evidence to elucidate these associations in the Chinese population.

Recently, the correlation between the efficacy of platinum-based chemotherapy and ERCC1 expression in patients with SCLC has attracted wide-spread attention, and a lot of investigations have been conducted, whereas conflicting results were presented. Therefore, we performed the present meta-analysis of eligible studies to derive a more precise evaluation of the association between ERCC1 expression and the clinical outcome in SCLC patients receiving platinum-based chemotherapy. A literature search for relevant studies was conducted in the electronic databases of PubMed, EMBASE and Web of Science. The inclusive criteria were SCLC patients treated by platinum-based chemotherapy, and evaluated the relationship between ERCC1 expression and the clinical outcomes [including overall response rate (ORR), overall survival (OS) or progression-free survival (PFS)]. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) was calculated to assess the risk. A total of nine studies including 1129 patients were included in final analysis. Our analysis indicated that positive/high ERCC1 expression was associated with unfavorable OS (HR = 1.18, 95%CI = 1.02-1.37) and PFS (HR = 1.46, 95%CI = 1.14-1.88). Subgroup analysis according to disease stage suggested the significant relationship was found in limited stage (LS-SCLC), but not in extensive stage (ES-SCLC). However, no significant association was found between ERCC1 expression and ORR. Our analysis suggested ERCC1 expression may be a prognostic factor in SCLC patients receiving platinum-based chemotherapy, especially for LS-SCLC.

We aimed to investigate the associations between polymorphisms of interleukin-1A (IL-1A), IL-1B, and IL-1 receptor antagonist (IL-1RN) and prostate cancer (PCa) risk.

The transforming growth factor-β1 (TGF-β1) gene 29 T/C polymorphism is thought to be associated with breast cancer risk. However, reports are largely conflicting and underpowered. We therefore conducted a meta- analysis of all available case-control studies relating the TGF-β1 29T/C polymorphism to the risk of developing breast cancer by including a total of 31 articles involving 24,021 cases and 31,820 controls. Pooled ORs were generated for the allele contrasts, with additive genetic, dominant genetic and recessive genetic models. Subgroup analysis was also performed by ethnicity for the TGF-β1 29T/C polymorphism. No association was found in the overall analysis (C vs T: OR=1.028, 95% CI=0.949-1.114, p-value 0.500; CC vs TC: OR=1.022, 95% CI=0.963- 1.085, p-value 0.478; CC vs TT: OR=1.054, 95% CI=0.898-1.236, p-value 0.522; CC vs TT+TC: OR=1.031, 95% CI=0.946-1.124, p-value 0.482; TT vs CC+TC: OR=0.945, 95% CI=0.827-1.080, p-value 0.403). Similarly, in the subgroup analysis by ethnicity, no association was found in Caucasian (C vs T: OR=1.041, 95% CI=0.932-1.162, p-value 0.475; CC vs TC: OR=1.031, 95% CI=0.951-1.118, p-value 0.464; CC vs TT: OR=1.081, 95% CI=0.865- 1.351, p-value 0.493; CC vs TT+TC: OR=1.047, 95% CI=0.929-1.180, p-value 0.453; TT vs CC+TC: OR= 0.929, 95% CI=0.775-1.114, p-value 0.429;) and Asian populations (C vs T: OR=1.004, 95% CI=0.908-1.111, p-value 0.931; CC vs TC: OR= 0.991, 95% CI=0.896-1.097, p-value 0.865; CC vs TT: OR=1.015, 95% CI=0.848-1.214, p-value 0.871; CC vs TT+TC: OR=1.000, 95% CI=0.909-1.101, p-value 0.994; TT vs CC+TC: OR= 0.967, 95% CI=0.808-1.159, p-value 0.720;). No evidence of publication bias was detected during the analysis. No significant association with breast cancer risk was demonstrated overall or on subgroup (Caucasian and Asian) analysis. It can be concluded that TGF-β1 29T/C polymorphism does not play a role in breast cancer susceptibility in overall or ethnicity-specific manner.

Previous studies have indicated that single nucleotide polymorphisms (SNPs) of the interleukin-17 (IL-17) gene are associated with an increased risk of gastric cancer. However, the findings were inconsistent.

Disrupted transforming growth factor- β (TGF-β) signaling is involved in the development of various types of cancer and the TGF-β receptor II (TGFBR2) is a key mediator of TGF-β growth inhibitory signals. It is reported that the G-875A polymorphism in TGFBR2 is implicated in risk of various cancers. However, results for the association between this polymorphism and cancer remain conflicting. To derive a more precise estimation, a meta-analysis of 3,808 cases and 4,489 controls from nine published case-control studies was performed. Our analysis indicated that G-875A is associated with a trend of decreased cancer risk for allele A versus(vs.) allele G [odds ratio (OR) =0.64, 95% confidence intervals (CI): 0.55-0.74], as well as for both dominant model [(A/ A+G/A) vs. G/G, OR=0.76, 95% CI: 0.64-0.90] and recessive model [A/A vs. (G/G+G/A), OR=0.74, 95% CI: 0.59-0.93). However, larger scale primary studies are required to further evaluate the interaction of TGFBR2 G-875A polymorphism and cancer risk in specific cancer subtypes.

To date, several studies have been conducted to assess the association between endothelial nitric oxide synthase (eNOS) gene 894G > T polymorphism and prostate cancer (PCa) risk, but the results are conflicting. To derive a more precise estimation of the relationship between 894G > T polymorphism and PCa risk, the present meta-analysis was performed. A total of eight case-control studies were included in this meta-analysis. The pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to evaluate the associations. Our results suggested that 894G > T polymorphism is associated with PCa risk under codominant (GT vs. GG) (OR = 1.11, 95 % CI = 1.01-1.22, P = 0.04) and overdominant (GT vs. GG + TT) (OR = 1.12, 95 % CI = 1.02-1.23, P = 0.02) models in the overall population, while there are no associations observed under dominant (GT + TT vs. GG), recessive (TT vs. GG + GT), and allelic (T vs. G) models. Moreover, when the eligible studies were stratified according to sources of control, significant association between 894G > T polymorphism and susceptibility of PCa was also identified under codominant (OR = 1.12, 95 % CI = 1.01-1.24, P = 0.03) and overdominant (OR = 1.13, 95 % CI = 1.02-1.25, P = 0.02) models when using healthy individuals as control. However, there are no significant associations found under any genetic models when using BPH patients as control group. In conclusion, the present meta-analysis suggested that the eNOS gene 894G > T polymorphism might be a risk factor in the onset of PCa.