Incidence and detection of high microsatellite instability in colorectal cancer in a Chinese population: a meta-analysis

BackgroundThe 4 most common types of DNA mutations in tumors are single-nucleotide variations, insertion-deletion, fusion, and copy number variations. This is followed by microsatellite instability (MSI), which is known to trigger the development of MSI-high (MSI-H) cancer and is responsible for 300,000 new cases of cancer per year in China. We aim to conduct a meta-analysis based on a comparison between the positive rates of the National Cancer Institute (NCI) panel (also known as 2B3D NCI panel) and mononucleotide panels for the diagnosis of MSI in the Chinese population.MethodsIn the present meta-analysis, we searched the PubMed, Embase, Web of Science, CNKI, Wanfang, CQVIP, and CBM databases. MSI diagnosis studies by PCR and capillary electrophoresis were included to compare the incidence of MSI-H in colorectal cancer obtained from panels with different microsatellite markers. Egger’s bias test was used to assess risk of bias.ResultsSeventeen articles were included, which used the Newcastle-Ottawa Scale (NOS) scale for quality evaluation. The NOS scores of the included documents were ≥7 points, and the quality of the documents met the requirements. The incidence of MSI-H detected by the 2B3D NCI panel was 13.5% [95% confidence interval (CI): 10.8–16.4, I²=52.321%, P=0.026, n=10 studies including 2,681 participants], the incidence of MSI-H detected by the mononucleotide panels was 10.6% (95% CI: 7.1–14.7, I²=81.147%, P=0.000, n=7 studies including 3,249 participants). This indicates that, in the Chinese population, the 2B3D NCI panel can detect 27.4% more MSI-H cancers than the mononucleotide panels, 54.7% more MSI-H cancers than the panel of 6 mononucleotides, and its sensitivity is comparable to that of Promega.ConclusionsThe findings of the meta-analysis demonstrated that, using the 2B3D NCI panel for MSI detection can avoid the underestimation of the incidence MSI-H in colorectal cancer and can be considered the most suitable panel for MSI detection in the Chinese population. The inclusion of only published data might be a potential source of publication bias.     

Adjuvant chemotherapy could improve the survival of pulmonary sarcomatoid carcinoma: A systematic review and meta-analysis

BackgroundComplete surgical removal is currently considered to be the best treatment option for pulmonary sarcomatoid carcinoma (PSC) especially in early stage operable disease; however, the reported recurrence-free survival is low. Benefits of adjuvant chemotherapy in PSC patients are still controversial, and there is no obvious agreement on the optimal treatment modalities of this disease. Therefore, we aimed to investigate the prognosis in terms of overall survival (OS) in patients with PSC who received adjuvant chemotherapy.MethodsThe review protocol was registered in PROSPERO (CRD42022306084). Patients with PSC who underwent surgical therapy with or without adjuvant chemotherapy were included into the meta-analysis. Hazard ratios (HR) with 95% confidence intervals (CIs) for OS were pooled and ROBINS-I tool was used to assess risk of bias of the included studies.ResultsWe identified four retrospective cohort studies with 6768 records from MEDLINE, Embase, and CENTRAL databases up to 9th September 2021, and altogether 1835 patients were included to the analysis. The present meta-analysis shows that patients receiving adjuvant chemotherapy had a significantly longer OS than patients who underwent surgical treatment alone (HR = 0.5657, 95%CI: 0.4391–0.7290, p < 0.0001).ConclusionsDespite the limited information on the chemotherapy regimens in the included studies, patients with PSC may benefit from adjuvant chemotherapy. More publications are required to evaluate and compare efficient adjuvant chemotherapy protocols in PSC cases.     

Poor oral health is associated with an increased risk of esophageal squamous cell carcinoma ‐ a population‐based case‐control study in China

To further examine the association between oral hygiene and esophageal squamous cell carcinoma (ESCC) risk and the effect modification of other exposures, we conducted a population‐based case‐control study between 2010 and 2012 in Taixing, China, a high‐risk area for ESCC. Cases were primarily recruited from endoscopy units at local hospitals, supplemented by linkage to the local Cancer Registry. Control subjects were frequency matched to cases by sex and age (5‐year groups) and were randomly selected from the Taixing Population Registry. For the current analysis, data from 616 histopathologically confirmed cases and 770 controls with complete information on oral hygiene were analyzed. Unconditional logistic regression models, including oral hygiene indicators and potential behavioral confounders, were used to derive odds ratios (ORs) and 95% confidence intervals (CIs). Tooth loss was only marginally significantly associated with ESCC risk (yes vs. no, OR = 1.29, 95% CI 0.94–1.74). However, the excess risk increased with increasing numbers of lost teeth (more than 6 teeth lost vs. none, OR = 1.48, 95% CI 1.04–2.11). Tooth brushing once or less per day, compared with tooth brushing twice or more per day, was associated with a 1.81‐fold increased risk of ESCC. In the stratification analyses, the increased risks associated with these indicators of oral health were more pronounced in older subjects (age ≥ 70 years), women, non‐smokers, and non‐drinkers. Further studies are warranted to verify these findings and to explore the underlying mechanisms, e.g., changed oral microbiota, associated with poor oral hygiene.     

The relationship between the number of circulating tumor cells and the prognosis in patients with esophageal squamous cell carcinoma

BackgroundEsophageal cancer (EC) is one of the most common malignancies worldwide, with high morbidity and mortality rates. Circulating tumor cell (CTC) detection has become a novel approach in clinical study of EC. In this study, the relationship between CTCs/c-Kit expression of CTCs and the prognosis of EC patients was analyzed in EC.MethodsA total of 43 EC patients with R0 resection were recruited for this study. The CanPatrol method was used to detect the CTC number in the peripheral blood of patients before and after operations, and the epithelial/interstitial type was classified. Multiple RNA in situ hybridization (RNA-ISH) was used to observethe c-Kit expression of CTCs. Post-operation follow-up occurred over 3 years. Logistic regression or the Cox proportional risk regression model was applied to analyze the relationship between CTC number, CTCs and disease characteristics, pathological stages and prognosis of patients with EC, and changes in CTCs before and after operations. c-Kit expression in different CTCs and the relationship between c-Kit expression and prognosis were also studied.ResultsThe detection rate of CTCswas 81% (35/43). The detection rates of epithelial-, mixed- and stromal-type CTCs were 53%, 63%, and 33%, respectively. The 3-year overall survival rate was 67%. A CTC level of >2 indicated an increased risk of recurrence, metastasis, and death (P=0.018, 0.002, respectively). Following the operations, the total number of CTCs decreased in 29 cases. Of these, 6 cases were unchanged, and 8 cases demonstrated elevated CTCs. There was a significant difference in the positive rate of mixed-type CTCs before and after the operations. The rate of c-Kit expression in CTCs of EC patients was 46% pre-operation. No statistically significant correlations were found between c-Kit expression and postoperative recurrence/metastasis/survival of EC patients.ConclusionsPreoperative CTC numbers, especially interstitial CTCs, were used as an auxiliary index in the prognosis of EC patients. The mRNA expression of c-Kit was detected in CTCs preoperatively in patients with EC, but no significant correlation between the c-Kit expression and the prognosis of EC patients was found.     

Association between XRCC3 T241M polymorphism and glioma risk: a meta-analysis

X-ray repair cross-complementing group 3 (XRCC3) plays a critical role in homologous recombination repair (HRR) accounting for repair of DNA double-strand breaks (DSB). Attention has been drawn upon the association of XRCC3 T241M polymorphism with glioma risk. The present meta-analysis aimed to examine whether XRCC3 T241M polymorphism was associated with glioma risk. Eligible articles were identified for the period up to March 2013. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were appropriately derived from fixed effects or random effects models. Eight case-control studies with a total of 3,455 glioma cases and 4,435 controls were included. Overall, no significant association between XRCC3 T241M polymorphism and glioma was found. In subgroup analysis, this polymorphism seemed to be associated with elevated glioma risk in Asians. No publication bias was detected. This meta-analysis suggested that XRCC3 T241M polymorphism did not confer glioma risk.     

The Glu298Asp polymorphism in the NOS3 gene and the risk of prostate cancer

The Glu298Asp polymorphism in the NOS3 gene has been implicated as a risk factor for prostate cancer. To date, several studies have evaluated the associations between the Glu298Asp polymorphism and prostate cancer risk; however, the results were inconclusive. The aim of the current study was to perform a meta-analysis to investigate the association between the polymorphism and the risk of prostate cancer. A total of 3,206 cases and 3,880 controls from eight case-control studies were included for data synthesis. The overall results suggested no significant association between the polymorphism and the risk of prostate cancer (OR=1.01, 95 % CI=0.92–1.11, p?=?0.83 for Asp/Asp+Glu/Asp vs. Glu/Glu). In the stratified analysis according to ethnicity, no significant associations were observed in Asians and Europeans. The current meta-analysis suggested that the Glu298Asp polymorphism of the NOS3 gene might not contribute to the risk of prostate cancer.     

The role of oral hygiene in head and neck cancer: results from International Head and Neck Cancer Epidemiology (INHANCE) consortium

BackgroundPoor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of five oral hygiene indicators with incident HNCs.MethodsIn a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), <5 missing teeth, tooth brushing at least daily, and visiting a dentist ≥once a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption.ResultsInverse associations with any HNC, in the hypothesized direction, were observed for <5 missing teeth [odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82], annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for ≤ 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer.ConclusionGood oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC.     

Quantitative evaluation of hepatitis B virus mutations and hepatocellular carcinoma risk: a meta-analysis of prospective studies

Background

The temporal relationship between hepatitis B virus (HBV) mutations and hepatocellular carcinoma (HCC) remains unclear.

Methods

We conducted a meta-analysis including cohort and nested case-control studies to prospectively examine the HCC risk associated with common variants of HBV in the PreS, Enhancer II, basal core promoter (BCP) and precore regions. Pertinent studies were identified by searching PubMed, Web of Science and the Chinese Biological Medicine databases through to November 2014. Study-specific risk estimates were combined using fixed or random effects models depending on whether significant heterogeneity was detected.

Results

Twenty prospective studies were identified, which included 8 cohort and 12 nested case-control studies. There was an increased risk of HCC associated with any PreS mutations with a pooled relative risk (RR) of 3.82 [95% confidence interval (CI): 2.59-5.61]. The pooled-RR for PreS deletion was 3.98 (95% CI: 2.28-6.95), which was higher than that of PreS2 start codon mutation (pooled-RR=2.63, 95% CI: 1.30-5.34). C1653T in Enhancer II was significantly associated with HCC risk (pooled-RR=1.83; 95% CI: 1.21-2.76). For mutations in BCP, statistically significant pooled-RRs of HCC were obtained for T1753V (pooled-RR=2.09; 95% CI: 1.49-2.94) and A1762T/G1764A double mutations (pooled-RR=3.11; 95% CI: 2.08-4.64). No statistically significant association with HCC risk was observed for G1896A in the precore region (pooled-RR=0.77; 95% CI: 0.47-1.26).

Conclusions

This study demonstrated that PreS mutations, C1653T, T1753V, and A1762T/G1764A, were associated with an increased risk of HCC. Clinical practices concerning the HCC risk prediction and diagnosis may wish to focus on patients with these mutations.     

Magnetic resonance elastography can predict the development of hepatocellular carcinoma: a meta-analysis and systematic review

BackgroundHepatocellular carcinoma (HCC) has become the third leading cause of cancer-related death worldwide, and its incidence rate is increasing. Magnetic resonance elastography (MRE) can indirectly realize the accurate non-invasive evaluation of liver reserve function in HCC patients. In this study, we aimed to evaluate the effectiveness of MRE in the diagnosis of HCC patients.MethodsWe searched globally-recognized electronic databases, such as PubMed, EMBASE, China National Knowledge Infrastructure, and Cochrane Central, for relevant literature on MRE prediction of HCC. The diagnostic performance of all studies was quantitatively summarized using a bivariate random effects model including heterogeneity analysis, receiver operating characteristic (ROC) curve, and bias determination.ResultsThe diagnostic accuracy of MRE for HCC was based on 1,735 patients. The sensitivity (31–100%) was lower than the specificity (81–94%). The overall sensitivity was 64% [95% confidence interval (CI): 46–79%; I²=92.44%], and the overall specificity was 85% (95% CI: 82–88%; I²=67.86%). Limited publication bias was observed in this study, and the sensitivity analysis showed that the study was robust.DiscussionThe results of our meta-analysis show that MRE has moderate sensitivity and excellent specificity in the detection of HCC. MRE can be an effective diagnostic tool for HCC and can provide strong support for the selection of clinical treatment methods and prognostic judgment.     

Oral health and risk of colorectal cancer: results from three cohort studies and a meta-analysis

BackgroundWhile studies have shown that poor oral health status may increase the risk of cancer, evidence of a specific association with the risk of colorectal cancer (CRC) is inconclusive. We evaluated the association between oral health and CRC risk using data from three large cohorts: the Shanghai Men's Health Study (SMHS), the Shanghai Women's Health Study (SWHS), and the Southern Community Cohort Study (SCCS), and carried out a meta-analysis of results from other relevant published studies.Patients and methodsThis study applied a nested case–control study design and included 825 cases/3298 controls from the SMHS/SWHS and 238 cases/2258 controls from the SCCS. The association between oral health status (i.e. tooth loss/tooth decay) and CRC risk was assessed using conditional logistic regression models. A meta-analysis was carried out based on results from the present study and three published studies.ResultsWe found that tooth loss was not associated with increased risk of CRC. ORs and respective 95% CIs associated with loss of 1–5, 6–10, and >10 teeth compared with those with full teeth are 0.87 (0.69–1.10), 0.93 (0.70–1.24), and 0.85 (0.66–1.11) among SMHS/SWHS participants; and 1.13 (0.72–1.79), 0.87 (0.52–1.43), and 1.00 (0.63–1.58) for those with loss of 1–4, 5–10, and >10 teeth among SCCS participants. Data regarding tooth decay were available in the SCCS, but were not associated with CRC risk. Meta-analysis confirmed the null association between tooth loss/periodontal disease and CRC risk (OR 1.05, 95% CI 0.86–1.29).ConclusionIn this analysis of three cohorts and a meta-analysis, we found no evidence supporting an association between oral health and CRC risk.     

Single nucleotide polymorphisms of ADH1B,ADH1C and ALDH2 genes and esophageal cancer: A population‐based case–control study in China

Alcohol drinking is a major risk factor for esophageal cancer (EC) and the metabolism of ethanol has been suggested to play an important role in esophageal carcinogenesis. Epidemiologic studies, including genomewide association studies (GWAS), have identified single nucleotide polymorphisms (SNPs) in alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) to be associated with EC. Using a population‐based case–control study with 858 EC cases and 1,081 controls conducted in Jiangsu Province, China, we aimed to provide further information on the association of ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms with EC in a Chinese population. Results showed that ADH1B (rs1229984) was associated with EC with odds ratios (ORs) of 1.34 [95% confidence interval (CI): 1.08–1.66] for G‐allele carriers compared to A/A homozygotes. No heterogeneity was detected on this association across different strata of alcohol drinking and tobacco smoking. Statistical interaction between ALDH2 (rs671) and alcohol drinking on EC susceptibility in both additive and multiplicative scales was observed. Compared to G/G homozygotes, A‐allele carriers were positively associated with EC among moderate/heavy drinkers (OR = 1.64, 95% CI: 1.12–2.40) and inversely associated with EC among never/light drinks (OR = 0.75, 95% CI: 0.54–1.03). In addition, statistical interaction between ALDH2 and ADH1B polymorphisms on EC susceptibility among never/light drinkers was indicated. We did not observe association of ADH1C polymorphism with EC. In conclusion, our findings indicated that ADH1B (rs1229984) was associated with EC independent of alcohol drinking and tobacco smoking status and alcohol drinking interacted with ALDH2 (rs671) on EC susceptibility in this high‐risk Chinese population.     

Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis

AimIt has been suggested that chronic hyperinsulinemia from insulin resistance is involved in the etiology of endometrial cancer (EC). We performed a systematic review and meta-analysis to assess whether insulin resistance is associated with the risk of EC.MethodsWe searched PubMed-Medline, Embase, Scopus, and Web of Science for articles published from database inception through 30th September 2014. We included all observational studies evaluating components defining insulin resistance in women with and without EC. Quality of the included studies was assessed by Newcastle–Ottawa scale. Random-effects models and inverse variance method were used to meta-analyze the association between insulin resistance components and EC.ResultsTwenty-five studies satisfied our inclusion criteria. Fasting insulin levels (13 studies, n = 4088) were higher in women with EC (mean difference [MD] 33.94 pmol/L, 95% confidence interval [CI] 15.04–52.85, p = 0.0004). No differences were seen in postmenopausal versus pre- and postmenopausal subgroup analysis. Similarly, non-fasting/fasting C-peptide levels (five studies, n = 1938) were also higher in women with EC (MD 0.14 nmol/L, 95% CI 0.08–0.21, p < 0.00001). Homeostatic model assessment - insulin resistance (HOMA-IR) values (six studies, n = 1859) in EC patients were significantly higher than in women without EC (MD 1.13, 95% CI 0.20–2.06, p = 0.02). There was moderate-to-high heterogeneity among the included studies.ConclusionCurrently available epidemiologic evidence is suggestive of significantly higher risk of EC in women with high fasting insulin, non-fasting/fasting C-peptide and HOMA-IR values.     

Association between glutathione S-transferase T1 null genotype and glioma susceptibility: a meta-analysis

The relationship between genetic polymorphisms of glutathione S-transferase (GST) and the development of glioma has been investigated in several epidemiologic studies. However, these studies report inconsistent results. In order to get this precise result, a meta-analysis was conducted by calculating the pooled odds ratios (OR) and the 95 % confidence intervals (95 % CI). Eleven case–control research studies with a total of 2,416 glioma cases and 4,850 controls were included into this meta-analysis. The combined results based on all studies showed that there was no significant association between the GSTT1 null allele and glioma risk (OR?=?1.188, 95 % CI?=?0.929–1.520, P _{heterogeneity}?=?0.003, P?=?0.170). In the subgroup analysis, the same results were found in our work. There was no risk of publication bias in this meta-analysis. Our results suggest that GSTT1 null genotype was not associated with the increased risk of glioma.     

Clinicopathological and prognostic significance of programmed death ligant-1 expression in gastric cancer: a meta-analysis

BackgroundGastric cancer (GC) is a common malignant tumor with a high incidence in China. The use of immune checkpoint inhibitors has become the focus of tumor immunotherapy in recent years. This study was to investigate the clinicopathological and prognostic significance of programmed death ligant-1 (PD-L1) expression in GC.MethodsWe searched the PubMed, ScienceNet, EMbase, CNKI, and Wanfang databases for retrospective cohort studies on the clinicopathology and prognosis of PD-L1 expression in GC published between January 2010 and April 2020. The literature was first selected to extract data according to the inclusion and exclusion criteria, then a meta-analysis performed using Stata15.0 software. Publication bias and sensitivity analysis were carried out for the included studies.ResultsA total of 3,218 patients in 15 studies were included in the meta-analysis. The positive expression of PD-L1 was related to a decrease in the 3-year survival rate (HR =1.32, 95% CI: 1.02–1.49, P=0.028) and 5-year survival rate (HR =1.39, 95% CI: 1.14–1.69, P=0.001). The difference in PD-L1 expression was related to lymph node metastasis (OR =1.73, 95% CI: 1.18–2.54, P<0.001), but not to tumor stage (OR =1.28, 95% CI: 0.81–2.02, P=0.292).ConclusionsThe results show that PD-L1 is related to the prognosis of GC. Its high expression decreases the 3- and 5-year survival rates and promotes lymph node metastasis, but does not reflect tumor stage. The results may provide a theoretical basis for the choice of clinical immunotherapy in GC patients.     

A systematic review and meta-analysis of the volume-outcome relationship in the surgical treatment of breast cancer. Are breast cancer patients better of with a high volume provider?

AimsTo conduct a systematic review of the literature on the volume-outcome relationship for the surgical treatment of breast cancer with consideration of the methodological quality of the available evidence and to perform a meta-analysis on the studies of considered good quality.MethodsA systematic search was done to identify all articles examining the effects of hospital or surgeon volume on clinical outcome of the surgical treatment of breast cancer. Reviews, opinion articles and surveys were excluded. All articles were critically appraised on methodological quality and risk of bias. After strict inclusion, meta-analysis assuming a random effects model was done to estimate the effect of higher hospital or surgeon volume on patient outcome.ResultsWe found 12 studies of good methodological quality which could be included for meta-analysis. The results showed a significant association between high volume providers and an improved survival. The association is the most robust for surgeon volume (HR 0.80 (0.71–0.90) and RR 0.85 (0.80–0.90). In addition there is an effect of hospital volume on the in-hospital mortality, although the mortality was very low (0.1–0.2%). Results of meta-analysis were heterogeneous. Sensitivity analysis showed a larger effect size for studies also adjusting for comorbidity for both studies on hospital and surgeon volume. The data were not suggestive for publication bias.ConclusionsThe results show that survival after breast cancer surgery is significantly associated with high volume providers.     

Prevalence of computed tomography-based sarcopenia and the prognostic value of skeletal muscle index and muscle attenuation amongst women with epithelial ovarian malignancy: A systematic review and meta-analysis

BackgroundSarcopenia represents an index of frailty amongst cancer patients and it is associated with poor oncological outcomes and a higher risk of surgical complications in several types of malignancy.AimTo further delineate the impact of sarcopenia assessed via computed tomography scan (CT) on oncological outcomes and post-operative complications amongst women with epithelial ovarian carcinoma (EOC). Our secondary objective was to quantify and understand the prevalence of sarcopenia in EOC.DesignWe systematically searched MEDLINE, SCOPUS, ClinicalTrials.gov, and Cochrane Database, from inception up to August 2021. Quality assessment was performed using the Newcastle-Ottawa scale (NOS). Outcomes consisted of prevalence, overall survival (OS), progression-free survival (PFS) and post-operative complications. Pooled analyses of proportion estimates, hazard ratios (HRs) and odds ratios (ORs) were performed with STATA and Review Manager 5.3.Results21 studies were included in this meta-analysis. NOS scores ranged from six to nine. Pooled analysis yielded an overall sarcopenia prevalence of 41%. Pooled analysis of adjusted HRs demonstrated significant association between low muscle attenuation (MA) [aHR = 1.23, (95% CI 1.02–1.47), p-value = 0.03] and OS, whilst low skeletal muscle index (SMI) trended towards shorter OS [aHR = 1.37, (95% CI 0.99–1.90), p-value = 0.05. Low-SMI was also associated with higher risk of total post-operative complications [uOR = 1.56, (95% CI 1.16–2.11), p-value = 0.004].ConclusionOur findings suggest that CT-assessed skeletal mass and radiodensity represent rather accurate indices of nutritional status and could prospectively be incorporated into the decision-making process in women with EOC.     

A microarray expression profile and bioinformatic analysis of circular RNA in human esophageal carcinoma

BackgroundRecent studies indicate that non-coding circular RNAs (circRNAs) are involved in the development of esophageal carcinoma (EC). This study aimed to identify differential expression of circRNAs in EC, which can provide potential biomarkers and therapeutic targets for EC treatment and improve the understanding of tumorigenesis mechanism.MethodsFirst, samples (n=5) of EC tissues and adjacent normal tissue were sent for circRNA microarray detection, Second, further bioinformatic analysis was performed, including circRNA-microRNA (miRNA), co-expression network analysis, Spearman correlation test, and cancer-related circRNA-miRNA axis analysis. Finally, the expression of circRNA that our analysis predicted to be hub genes was verified in samples (n=15) of EC tissues and adjacent normal tissue by real-time polymerase chain reaction (RT-PCR).ResultsMicroarray identified 102 upregulated and 67 significantly downregulated circRNAs were in EC patients’ tumors relative to adjacent normal tissue. One upregulated circRNA (hsa_circRNA_401955) showed the most connection with MREs, therefore was regarded as the hub gene by the Spearman correlation test. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that four primary pathways (mRNA surveillance, cytoskeleton actin regulation, spliceosome, and the NOD-like receptor signaling pathway) were predicted in the hub circRNA’s five connected miRNA response elements (MREs). Furthermore, cancer-related circRNA-miRNA axis analyses showed that hsa_circRNA_100375 and its four connected MREs participated in the cancer-related pathway. RT-PCR showed that hsa_circRNA_100375 and hsa_circRNA_401955 were significantly increased in the tumor tissues of EC patients.ConclusionsAbnormal expression of circRNAs was involved in the tumorigenesis of EC. Key circRNAs, namely hsa_circRNA_401955 and hsa_circRNA_100375, may be as potential biomarkers and therapeutic targets for the treatment of EC.     

Common Variants in the PALB2 Gene Confer Susceptibility to Breast Cancer: a Meta-analysis

Objective: Increasing scientific evidence suggests that common variants in the PALB2 gene may confersusceptibility to breast cancer, but many studies have yielded inconclusive results. This meta-analysis aimed toderive a more precise estimation of the relationship between PALB2 genetic variants and breast cancer risk.Methods: An extensive literary search for relevant studies was conducted in PubMed, Embase, Web of Science,Cochrane Library, CISCOM, CINAHL, Google Scholar, CNKI and CBM databases from their inception throughSeptember 1st, 2013. A meta-analysis was performed using the STATA 12.0 software and crude odds ratios (ORs)with 95% confidence intervals (CIs) were calculated. Results: Six case-control studies were included with a totalof 4,499 breast cancer cases and 6,369 healthy controls. Our meta-analysis reveals that PALB2 genetic variantsmay increase the risk of breast cancer (allele model: OR>1.36, 95%CI: 1.20~1.52, P < 0.001; dominant model:OR>1.64, 95%CI: 1.42~1.91, P < 0.001; respectively). Subgroup analyses by ethnicity indicated PALB2 geneticvariants were associated with an increased risk of breast cancer among both Caucasian and Asian populations(all P < 0.05). No publication bias was detected in this meta-analysis (all P > 0.05). Conclusion: The currentmeta-analysis indicates that PALB2 genetic variants may increase the risk of breast cancer. Thus, detection ofPALB2 genetic variants may be a promising biomarker approach.