Major histocompatibility complex class I-related chain A (MICA) is considered as a tumor antigen, and its expression is affected by its genetic polymorphisms. However, the relationship between rs2596542 polymorphisms in MICA promoter region and hepatocellular carcinoma (HCC) is not fully elucidated so far. This study aims to explore the relationship between single nucleotide polymorphism of rs2596542 and the risk of HCC development through meta-analysis.

Several studies detected abnormal mi-RNAs expression levels in childhood Acute Lymphoblastic Leukemia (ALL) with potential diagnostic value. We conducted a systematic search on certain microRNAs in childhood ALL. We included 17 studies with a total of 928 ALL children and 307 controls. Ten studies provided miRNAs expression levels and seven provided frequency data. Sensitivity and specificity of a single miRNA ranged from 46.55% to 100% and from 71.8% to 100%, respectively. The highest diagnostic odds ratio (DOR) was for the diagnostic panel (miR-128a and miR-223) reaching 546 [95% CI: 73.768-4041.282]. Also, miR-128a, miR-128b, miR-223, let-7b, miR-155 and miR-24 can be used as diagnostic discriminatory biomarkers between ALL and AML. Further large cohort studies are needed to confirm our results.

Alcohol consumption has been established to be a major factor in the development and progress of cancer. Genetic polymorphisms of alcohol-metabolism genes result in differences between individuals in exposure to acetaldehyde, leading to possible carcinogenic effects. Arg47His (rs1229984 G > A) in ADH1B have been frequently studied for its potential effect on carcinogenesis. However, the findings are as yet inconclusive. To gain a more precise estimate of this potential association, we conducted a meta-analysis including 66 studies from 64 articles with 31999 cases and 50964 controls. The pooled results indicated that ADH1B Arg47His polymorphism is significantly associated with the decreased risk of overall cancer (homozygous model, odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.49-0.77; heterozygous model, OR = 0.71, 95% CI = 0.60-0.84; recessive model, OR = 0.83, 95% CI = 0.76-0.91; dominant model, OR = 0.62, 95% CI = 0.53-0.72; and allele comparison, OR = 0.82, 95% CI = 0.75-0.89). Stratified analysis by cancer type and ethnicity showed that a decreased risk was associated with esophageal cancer and head and neck cancer amongst Asians. In conclusion, our meta-analysis suggested that ADH1B Arg47His polymorphism was significantly associated with decreased overall cancer risk. These findings need further validation in large multicenter investigations.

A germline deletion in BIM (B cell lymphoma-2-like 11) gene has been shown to impair the apoptotic response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in vitro but its impact on response to EGFR-TKIs in patients of nonsmall cell lung cancer (NSCLC) remains controversial.

The relationship between gender and kidney cancer incidence/outcomes has been largely evaluated and may significantly impact the management of patients diagnosed with these tumors. We reviewed and summarized the most relevant recent publications reporting about this clinically meaningful relationship.

Vascular endothelial growth factor (VEGF) gene plays a key role in angiogenesis and tumor growth. The relationship between VEGF gene polymorphisms and bladder cancer (BCa) risk was studied extensively in recent years. However, the currently available results are controversial. To ascertain whether VEGF polymorphisms are associated with the susceptibility to BCa, we conducted this systematic review and meta-analysis.

To systematically analyze CT and clinical characteristics to find out the risk factors of epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC). Then the significant characteristics were used to set up a mathematic model to predict EGFR mutation in NSCLC.

This study aims to determine the association of EGFR/KRAS mutation status with histological subtypes of lung adenocarcinoma (LAC) based on the IASLC/ATS/ERS classification.

Background: Cancer-related cognitive impairment (CRCI) is a commonly reported complaint among non-CNS cancer patients. Even subtle CRCI may have detrimental effects on quality of life and identifying patients at increased risk for CRCI to improve survivorship care is important. In the present paper, we systematically reviewed available studies of possible genetic risk factors for developing CRCI. Methods: Keyword-based systematic searches were undertaken on 24 July 2018 in PubMed, Web of Science, The Cochrane Library, and CINAHL. Three authors independently evaluated full-texts of identified papers and excluded studies with registration of reasons. Seventeen studies reporting results from 14 independent samples were included for review. Two authors independently quality assessed the included studies. The review was preregistered with PROSPERO (CRD42018107689). Results: Ten studies investigated apolipoprotein E (APOE), with four studies reporting that carrying at least one risk allele (APOE4 (ε4)) was associated with CRCI, while six studies found no association. The remaining identified genetic risk variants associated with CRCI located in: COMT, four DNA repair genes, five oxidative stress genes, 22 genes related to breast cancer phenotype, and GNB3. No associations were found between CRCI and genes coding for interleukin-6 (IL6), tumor necrosis factor alpha (TNF), interleukin 1 beta (IL1B), and brain-derived neurotropic factor (BDNF). With the exception of APOE, the genetic risk factors had only been investigated in one or two studies each. Conclusions: Overall, the available evidence of possible genetic risk factors for CRCI is limited. While some research suggests a role for the ε4 allele, the literature is generally inconsistent, and the currently available evidence does not allow clear-cut conclusions regarding the role of genetic factors in the development of CRCI. Larger genetic studies and studies investigating additional genetic variants are needed to uncover genetic risk factors for CRCI.

Accumulating evidence supports the overexpression of mucin 1 (MUC1) in colorectal cancer (CRC), but the value of elevated MUC1 expression remains controversial. Here, we evaluated the prognostic and clinicopathological value of MUC1 expression in CRC.

Serrated adenomas are genetically heterogeneous, and the histological classification into sessile serrated (SSA) adenoma and traditional serrated adenoma (TSA) does not reflect the molecular landscape. The objective of this study was to assess clinical or pathological factors associated with BRAF-V600E mutation in serrated adenomas. Systematic review and meta-analysis was performed by searching electronic databases from January 2011 to January 2019 for studies assessing the association of BRAF-V600E mutation with clinical or pathological features of serrated adenomas. Odds ratio (OR) was calculated for each factor; a P-value <0.05 was considered significant. Forty studies assessing 3511 serrated adenomas (2375 SSAs and 1136 TSAs) were included. BRAF-V600E mutation was significantly associated with proximal localisation (OR = 2.71; P < 0.00001) and CIMP-H status (OR = 4.81; P < 0.0001) in both SSA and TSA, with polyp size <10 mm (OR = 0.41; P = 0.02) in TSA, and with endoscopic pit pattern II-O (OR = 13.11; P < 0.00001) and expression of MUC5A5 (OR = 4.43; P = 0.003) and MUC6 (OR = 2.28; P < 0.05) in SSA. Conversely, BRAF mutation was not associated with age <70 years (OR = 1.63; P = 0.34), age <60 years (OR = 0.86; P = 0.79), female sex (OR = 0.77; P = 0.12), flat morphology (OR = 1.52; P = 0.16), presence of any dysplasia (OR = 1.01; P = 0.59), serrated dysplasia (OR = 1.23; P = 0.72) and invasive cancer (OR = 0.67; P = 0.32), nuclear β-catenin expression (OR = 0.73; P = 0.21) and p53 overexpression (OR = 1.24; P = 0.82). In conclusion, BRAF-V600E mutation is associated with proximal localisation and CIMP-H status in both SSA and TSA, with size <10 mm only in TSA, and with expression of MUC5A5 and MUC6 and endoscopic pit pattern II-O at least in SSA. In serrated adenomas, BRAF-V600E mutation does not seem to be associated with age and sex, with the prevalence of dysplasia and cancer and with the morphology of the dysplastic component.

The preferred type of postremission therapy (PRT) for intermediate-risk acute myeloid leukemia (AML) in first complete remission (CR1) is a subject of continued debate. Although allogeneic stem cell transplantation (alloSCT) is regarded as a curative strategy for AML, the efficacy of autologous stem cell transplantation (autoSCT) for patients without a matched sibling donor (MSD) has remained controversial.

High-risk non-muscle-invasive bladder cancer (HR-NMIBC) represents over 30% of all incident urothelial bladder cancers (BCs); patients are at risk of progression, and 20-30% will die from BC within 5 yr. Current guidelines recommend induction and maintenance of intravesical bacillus Calmette-Guérin (BCG) or upfront radical cystectomy for highest-risk disease, treatments with markedly different morbidity, mortality, and patient burden. There are no validated biomarkers to facilitate such treatment decisions. Alterations in DNA methylation are commonplace in BC; hence, measurable changes in DNA methylation represent an opportunity for the discovery of such biomarkers.

Background The prognostic value of TP53 commutation in epidermal growth factor receptor (EGFR) mutant lung cancer is controversial and we therefore conducted this systematic review and meta-analysis. Methods A systematic search was carried out in Pubmed, Web of Science, the Cochrane Library, Medline and Embase up to 19 April 2018. The pooled hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS), the relative risk (RR) of objective response rate (ORR) were calculated. Results Overall, a total of eight studies comprising 2979 patients were included. When generally comparing TP53 mutation group with TP53 wild-type group, we confirmed the prognostic value of poor OS of TP53 in EGFR mutant lung cancers (HR 1.73, 95% CI 1.22-2.44, P = 0.002). In subgroup analysis of OS, the prognostic value was maintained in patients treated with EGFR tyrosine kinase inhibitors (TKIs) but not in those treated with non-targeted therapy (HR 2.29, 95% CI 1.39-3.76, P = 0.001), and was also maintained in patients with advanced-stage lung cancers rather than those of all stages (HR 2.00, 95% CI 1.11-3.61, P = 0.021). For patients treated with EGFR TKIs, TP53 commutation was predictive of a poor PFS (HR 2.18, 95% CI 1.42-3.36, P < 0.001) but the prognostic value on ORR was not observed (RR 1.15, 95% CI 0.92-1.44, P = 0.212). Additional subgroup analysis based on TP53 mutation subtypes was not pooled due to limited data. Conclusion Generally we confirmed the prognostic value of poor OS and PFS of TP53 commutation in EGFR mutant lung cancers, and it should be further investigated and validated regarding the prognostic role of TP53 mutation subtypes.

The spectrum of treatment options for patients with metastatic BRAF-mutated melanoma is broad, spanning multiple treatment classes. However, there is a lack of head-to-head evidence comparing targeted and immunotherapies. The purpose of this study is to conduct a network meta-analysis (NMA) in previously untreated, BRAF-mutated melanoma patients and estimate the relative efficacy of systemic therapies for this patient population at the treatment level.

The association of ABO blood groups with gastric cancer risk was proposed decades ago, but the results have been inconsistent.

Telomerase activity and (human) Telomerase Reverse Transcriptase (hTERT) expression are considered hallmarks in oncogenesis of neoplasms and are upregulated by alterations of the hTERT promoter. In meningiomas, numerous studies investigated hTERT expression, telomerase activity, promoter mutations, and methylations. Moreover, reports about hTERT-targeted chemotherapy in meningiomas have recently been published. We provide a systematic review of the literature about the role of hTERT in meningiomas. TERT expression and telomerase activity is found in benign and high-grade meningiomas and increase with WHO grade. Remarkably, rates of TERT expression/telomerase activity usually exceed mutation frequency and both telomerase activity and TERT expression have also been found in hTERT promoter wildtype meningiomas, indicating further mechanisms of TERT upregulation. Although hTERT promoter methylation has been reported in the vast majority of meningiomas, correlation with TERT expression remains controversial. Rates of promoter mutations, and methylation were shown to increase with rising WHO grade. Moreover, promoter methylation and mutations strongly correlate with prognosis. Although mutations predicted malignant progression, de novo mutations in high-grade recurrences of former benign lesions were also observed. Retroviral transduction of the TERT gene enabled immortalization in several grade I-III meningioma cell lines. In vitro analyses revealed significant effects on viability in hTERT-mutated meningioma cells after targeted treatment. Alternative mechanisms of telomere lengthening are usually absent in meningiomas. TERT and hTERT promoter alterations play a major role during oncogenesis of meningiomas with implications for prognosis and potentially treatment.

The role of forkhead box P3 (FOXP3) protein in tumorigenesis has long been controversial and existing data on the association between FOXP3 gene polymorphisms and cancer susceptibility were inconsistent. Here, we conducted a meta-analysis to better clarify the relationship. A comprehensive search of studies published from July 2008 to June 2018 was conducted. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs) were performed using the Revman 5.2 software. A total of 12 articles with 19 case-control studies and 10389 participants were included. Three FOXP3 polymorphisms and six cancer types were evaluated. While no significant results were observed in overall and breast cancer groups for rs3761548 (A/C) polymorphisms, the pooled data showed an elevated risk of cancer in variant AA genotypes and A allele for Chinese population (AA vs. AC+CC: OR = 1.61, 95% CI = 1.09, 2.39; AA vs. CC: OR = 1.74, 95% CI = 1.05, 2.89; A vs. C: OR = 1.34, 95% CI = 1.00, 1.78). Neither the overall group analyses nor the subgroup analyses stratified by cancer type and ethnicity proposed any significant association of rs2280883 (C/T) and rs3761549 (T/C) polymorphisms with cancer susceptibility. This meta-analysis suggested that FOXP3 rs3761548 (A/C) polymorphisms were associated with increased cancer risk in Chinese population while rs2280883 (C/T) and rs3761549 (T/C) polymorphisms were not. More large-sample researches with diverse ethnicities and cancer types are needed to draw a concrete conclusion.

A genetic component is accepted in the etiology of the glioma. Evidence from candidate genes studies and GWAS reveal that CCDC26 gene could increase the risk of glioma. We performed a systematic review and up-to-date meta-analysis to explore if polymorphisms of CCDC26 gene (rs891835, rs6470745, and rs55705857) may be a susceptibility factor in developing glioma. An online search in PubMed, Web of Science, and SCOPUS up to September 2018 was performed. The pooled odds ratios were evaluated by fixed effects model and random effects model. Analyses of the overall sample and ethnic sub-groups were performed. In all the analyses, the allelic, additive, dominant, and recessive models were used. We found an association between all polymorphisms evaluated and an increased risk for glioma in the overall population in all the models studied. In sub-group analysis, we found that rs891835 and rs6470745 increased the risk of glioma in Europeans and Caucasians. On the other hand, the rs891835 polymorphism did not reveal any statistical association in Chinese population. Taken into consideration the limitations of this study, the present findings suggest a possible participation of rs891835, rs6470745, and rs55705857 as risk factors to develop glioma. Furthermore, it is possible that the involvement of CCDC26 variants depends on ethnicity. However, we recommend to perform further studies to have conclusive outcomes.

The aim of the present study was to map and grade evidence for the relationships between telomere length with a diverse range of health outcomes, using an umbrella review of systematic reviews with meta-analyses. We searched for meta-analyses of observational studies reporting on the association of telomere length with any health outcome (clinical disease outcomes and intermediate traits). For each association, random-effects summary effect size, 95% confidence interval (CI), and 95% prediction interval were calculated. To evaluate the credibility of the identified evidence, we assessed also heterogeneity, evidence for small-study effect and evidence for excess significance bias. Twenty-one relevant meta-analyses were identified reporting on 50 different outcomes. The level of evidence was high only for the association of short telomeres with higher risk of gastric cancer in the general population (relative risk, RR = 1.95, 95%CI: 1.68-2.26), and moderate for the association of shorter telomeres with diabetes or with Alzheimer's disease, even if limited to meta-analyses of case-control studies. There was weak evidence for twenty outcomes and not significant association for 27 health outcomes. The present umbrella review demonstrates that shorter telomere length may have an important role in incidence gastric cancer and, probably, diabetes and Alzheimer's disease. At the same time, conversely to general assumptions, it does not find strong evidence supporting the notion that shorter telomere length plays an important role in many health outcomes that have been studied thus far.