It has been suggested that long non-coding RNA (lncRNA) gene polymorphisms are associated with cancer risk. In this article, we conducted a systematic review related to studies on the association between lncRNA single-nucleotide polymorphisms (SNPs) and the overall risk of cancer. A total 17 SNPs in four common lncRNA genes were included in the meta-analysis. In the lncRNA H19, the rs2735971 A/G, rs2839698C/T, and rs3024270 G/C polymorphisms, but not rs217727C/T, were correlated with overall cancer risk. The results also suggested that other SNPs were correlated with overall cancer risk, namely, two in HOTAIR (HOX transcript antisense RNA: rs920778C/T and rs7958904 G/C) and two in PRNCR1 (rs1016343C/T and rs16901946 A/G). No association was found between the three ZNRD1-AS1 (ZNRD1 antisense RNA 1) SNPs and the risk of cancer. In summary, our findings suggest that quite a few studied lncRNA SNPs are associated with overall cancer risk; therefore, they are potential predictive biomarkers for the risk of cancer. Moreover, other lncRNA SNPs investigated were also relevant to cancer but studies on them are limited, and they were also briefly reviewed as candidate cancer markers.

microRNAs are widely involved in a variety of life processes and considered as potential biomarkers of tumor prognosis. A growing number of studies have documented that miRNAs were associated with outcome in NSCLC patients and can act as a prognostic marker. However, existing studies concerning the relationship between miRNAs and outcome in NSCLC patients were contentious and dispersive. Therefore, a systematic metaanalysis to explore the prognostic value of miRNAs on NSCLC patients is urgently needed.

MicroRNAs (miRNAs) play important roles in cancer development. MiR-222, which is deregulated in multiple types of cancers, shows potential as a prognostic biomarker; however, the association between miR222 expression and cancer prognosis was controversial in previous studies. Here we analyzed the relationship between miR-222 and the survival of cancer patients.

Purpose: Androgen receptor (AR) expression has been observed in about 70% of patients with breast cancer, but its prognostic role remains uncertain.Experimental Design: To assess the prognostic role of AR expression in early-stage breast cancer, we performed a meta-analysis of studies that evaluated the impact of AR at the protein and gene expression level on disease-free survival (DFS) and/or overall survival (OS). Eligible studies were identified by systematic review of electronic databases using the MeSH-terms "breast neoplasm" and "androgen receptor" and were selected after a qualitative assessment based on the REMARK criteria. A pooled gene expression analysis of 35 publicly available microarray data sets was also performed from patients with early-stage breast cancer with available gene expression and clinical outcome data.Results: Twenty-two of 33 eligible studies for the clinical meta-analysis, including 10,004 patients, were considered as evaluable for the current study after the qualitative assessment. AR positivity defined by IHC was associated with improved DFS in all patients with breast cancer [multivariate (M) analysis, HR 0.46; 95% confidence interval (CI) 0.37-0.58, P < 0.001] and better OS [M-HR 0.53; 95% CI, 0.38-0.73, P < 0.001]. Thirty-five datasets including 7,220 patients were eligible for the pooled gene expression analysis. High AR mRNA levels were found to confer positive prognosis overall in terms of DFS (HR 0.82; 95% CI 0.72-0.92;P = 0.0007) and OS (HR 0.84; 95% CI, 0.75-0.94; P = 0.02) only in univariate analysis.Conclusions: Our analysis, conducted among more than 17,000 women with early-stage breast cancer included in clinical and gene expression analysis, demonstrates that AR positivity is associated with favorable clinical outcome. Clin Cancer Res; 23(11); 2702-12. ©2016 AACR.

Pancreatic cancer is one of the deadliest cancers worldwide, and life expectancy after diagnosis is often short. Most pancreatic tumours appear sporadically and have been highly related to habits such as cigarette smoking, high alcohol intake, high carbohydrate, and sugar consumption. Other observational studies have suggested the association between pancreatic cancer and exposure to arsenic, lead, or cadmium. Aside from these factors, chronic pancreatitis and diabetes have also come to be considered as risk factors for these kinds of tumours. Studies have found that 10% of pancreatic cancer cases arise from an inherited syndrome related to some genetic alterations. One of these alterations includes mutation in BRCA2 gene. BRCA2 mutations impair DNA damage response and homologous recombination by direct regulation of RAD51. In light of these findings that link genetic factors to tumour development, DNA damage agents have been proposed as target therapies for pancreatic cancer patients carrying BRCA2 mutations. Some of these drugs include platinum-based agents and PARP inhibitors. However, the acquired resistance to PARP inhibitors has created a need for new chemotherapeutic strategies to target BRCA2. The present systematic review collects and analyses the role of BRCA2 alterations to be used in early diagnosis of an inherited syndrome associated with familiar cancer and as a prognostic and predictive biomarker for the management of pancreatic cancer patients.

ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA.

Microsomal epoxide hydrolase (mEH) is a crucial biotransformation enzyme that has capability to metabolize a large number of structurally divergent, highly reactive epoxides, and numerous environmentally exposed carcinogens. It catalyzes the conversion of xenobiotic epoxide compounds into more polar diol metabolites and may play important part of the enzymatic defense against adverse effects of foreign compounds. Most commonly, two functional polymorphisms affecting mEH enzyme activity have been identified: One in exon 3 and other in exon 4 of the mEH gene, which results in His113Tyr and Arg139His amino acid substitutions, respectively. Recent reports have shown that polymorphisms in mEH gene loci may an important risk factor for susceptibility of prostate cancers (PCs), worldwide, but inconsistent finding were also be illustrated. To the best of our knowledge, globally, there is no any systematic review has been published related to mEH gene polymorphisms and PC risk. Thus, in the current review, we have discussed the association between mEH gene polymorphisms, gene-environmental interaction, and PC risk.

Colorectal cancer (CRC) is one of the leading cause of cancer deaths worldwide. Since CRC is largely asymptomatic until alarm features develop to advanced stages, the implementation of the screening programme is very much essential to reduce cancer incidence and mortality rates. CRC occurs predominantly from accumulation of genetic and epigenetic changes in colon epithelial cells, which later gets transformed into adenocarcinomas.

Tat-interacting protein 30 (TIP30) is a tumor suppressor protein that has been found to be expressed in a wide variety of tumor tissues. TIP30 is involved in the control of cell apoptosis, growth, metastasis, angiogenesis, DNA repair, and tumor cell metabolism. The methylation of the TIP30 promoter is also associated with tumor prognosis. To evaluate this topic further, we conducted a systematic meta-analysis to explore the clinicopathological and prognostic significance of TIP30 for tumor patients.

Pediatric head and neck Squamous cell carcinoma (PHNSCC) is a rare disease. The optimum treatment and outcome remains poorly understood because of rarity.

Primary care providers (PCPs) can play a critical role in helping patients receive the preventive health benefits of cancer genetic risk information. Thus, the objective of this systematic review was to identify studies of US PCPs' knowledge, attitudes, and communication-related behaviors regarding genetic tests that could inform risk-stratification approaches for breast, colorectal, and prostate cancer screening in order to describe current findings and research gaps.

Already the fourth most common cancer in women in the developed world, the incidence of endometrial cancer is increasing rapidly, in line with the increasing prevalence of obesity. Relatively few studies have been undertaken of risk-reducing interventions aimed at limiting the impact of the disease on both individuals and the health service. Those that have been performed have demonstrated only modest results due to their application in relatively unselected populations. A validated risk prediction model is therefore urgently required to identify individuals at particularly high risk of endometrial cancer who may benefit from targeted primary prevention strategies and to guide trial eligibility. On the basis of a systematic review of the literature, the evidence for inclusion of measures of obesity, reproduction, insulin resistance, and genetic risk in such a model is discussed, and the strength of association between these risk factors and endometrial cancer is used to guide the development of a pragmatic risk prediction scoring system that could be implemented in the general population. Provisional cutoff values are described pending refinement of the model and external validation in large prospective cohorts. Potential risk-reducing interventions are suggested, highlighting the need for future studies in this area if the increasing tide of endometrial cancer is to be stemmed. Cancer Prev Res; 10(1); 1-13. ©2016 AACR.

Oral verrucous carcinoma (OVC), a low-grade variant of oral squamous cell carcinoma (OSCC), is most frequently seen in the oral cavity. No clear etiology has been found for this lesion, but human papilloma virus, chewing betel nuts, and ultraviolet radiation are suggested as probable causes. Differential diagnosis of OVC is challenging for oral pathologists. The aim of this study was to review the molecular-based approaches for differential diagnosis of OVC. An electronic search was conducted in Medline and Scopus from January 2004 to July 2015 limited to English language publications. Published papers on verrucous carcinoma (VC) were found according to the inclusion and exclusion criteria and analyzed qualitatively. Data extraction were performed according to PRISMA statement. A total of 423 articles were reviewed; out of which, 26 articles completely fulfilled the inclusion criteria. Most of the included studies investigated proliferative and apoptotic biomarkers such as p53 and Ki67. No definite conclusion was drawn for cytoskeletal biomarkers due to variability of factors and lack of significant expression. However, it seems that cytokeratin10 (CK 10) can be useful for differentiation of OVC and benign squamous lesions. Among cell surface and extracellular matrix biomarkers tissue biomarkers, matrix metalloproteinase (MMP)-2, -9, CD31 and CD68 seem to be useful for differentiation of OVC and OSCC and glucose transporter-1 (GLUT-1) can help in differentiation of OVC from oral epithelial dysplasia. Differences among OVC, OSCC and normal epithelium in expression profiles of the investigated biomarkers help in their differential diagnosis; although, clinicohistopathological similarities among verrucous hyperplasia, noninvasive OVC and invasive well-differentiated OSCC make the diagnosis difficult. Further studies are required to better differentiate these oral lesions.

Thyroid nodules are usually diagnosed using fine-needle aspiration (FNA). The sensitivity limitations of FNA result in 10-30% of nodules being classified as "indeterminate". The BRAFV600E mutation is associated with papillary thyroid carcinoma (PTC). We conducted a systemic review and meta-analysis to evaluate the diagnostic utility of the BRAFV600E mutation in indeterminate nodules.

Various literatures have demonstrated that overexpression of Metadherin (MTDH) is correlated with tumor metastasis and it can predict poor survival outcomes in female reproduction malignancies. In order to enhance the statistical power and reach a recognized conclusion, we conducted a systematic review and meta-analysis to thoroughly investigate the association of MTDH expression with tumor metastasis and survival outcomes following PRISMA guidelines. Odds ratios (ORs) and hazard ratios (HRs) were used to demonstrate the impact of MTDH on tumor metastasis and prognosis respectively. Data were pooled with appropriate effects model on STATA12.0. Our results indicated that high MTDH expression is significantly correlated with higher mortality for breast, ovarian and cervical cancer. High immunohistochemical expression of MTDH is remarkably associated with shorter disease-free survival (DFS) in breast cancer but not in ovarian cancer. The pooled results suggested that high level of MTDH significantly predicted distant metastasis and lymph node metastasis in breast cancer. Strong associations were observed between MTDH expression and lymph node metastasis in ovarian and cervical cancer. In conclusion, MTDH might be a novel biomarker which can effectively reflect metastasis status and prognosis of breast cancer. However, its application in clinical practice needs more prospective studies with large samples.

Methylation of tumor suppressor gene promoter leads to transcription inactivation and is involved in tumorigenesis. Several studies demonstrate a potential association between the Death-Associated Protein Kinase (DAPK) gene promoter methylation and bladder cancer risk, tumor stage and histological grade. Due to inconsistent results of these studies, we performed this meta-analysis to ascertain the association.

There is considerable evidence regarding the efficacy and effectiveness of BRCA genetic testing programs, but whether they represent good use of financial resources is not clear. Therefore, we aimed to identify the main health-care programs for BRCA testing and to evaluate their cost-effectiveness.

Studies of germline polymorphisms as predictors of tumor response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody agents in metastatic colorectal cancer have reported inconsistent results. We performed a systematic review of studies from 1990 to September 2015, followed by random-effects meta-analyses for polymorphisms examined in at least three studies. Of 87 studies, 40 passed the criteria for systematic review and 23 for meta-analysis. The polymorphisms suitable for meta-analysis were CCND1 (rs17852153), COX2 (rs20417), EGF (rs4444903), EGFR (rs712829, rs11543848, 3'UTR CA repeat), FCGR2A (rs1801274), FCGR3A (rs396991), IL8 (rs4073), KRAS (rs61764370) and VEGFA (rs3025039). Meta-analysis yielded nominal significance (at α=0.05) for rs4444903 and rs11543848, but showed no significant results after multiple testing correction; this was unchanged by sensitivity analyses to address subgroups, funnel-plot asymmetries, and study quality. This highlights a tendency for lack of replication in the face of initial positive results, and possibly the unsuitability of relying on tumor response as a surrogate marker in this setting.

Purpose. We aimed to comprehensively review contemporary literature on genetic and epigenetic biomarkers associated with the prediction of Bacillus Calmette-Guerin (BCG) response after the transurethral resection of a bladder tumor and to discuss the application of these biomarkers in precision cancer care for bladder cancer. Method. We performed a systematic review of published literatures in the databases PubMed and Embase by using the following key words: bladder cancer, BCG, gene, and methylation. Studies associated with cell lines, animal models, and muscle invasive bladder cancer were excluded. Results. The genetic variations associated with BCG response can be classified into three categories: germline variations, somatic variations, and epigenetic alterations. Genes related to BCG response were mainly involved in single-nucleotide polymorphisms, copy number variations, and gene methylations. Conclusions. Although these gene alterations are currently the most promising predictive markers of BCG response, most studies about bladder cancer DNA biomarkers are related to germline variations in candidate genes, and the results are not consistent. Only one study is related to somatic variation, and further evaluation in large-scale validation studies should be conducted to assess the potential clinical application of these findings. In addition, other biomarkers based on different "-omics" technologies should be considered in future studies.

Multiple studies have investigated global DNA methylation profiles and gene-specific DNA methylation in blood-based DNA to develop powerful screening markers for cancer. This systematic review summarizes the current evidence on methylation studies that investigated methylation level of blood-derived DNA of breast cancer (BC) patients in comparison to healthy controls by conducting a systematic literature review in PubMed and Web of Science. Essential results, such as methylation levels of BC cases and healthy controls, p values, and odds ratios, were extracted from these studies by two investigators independently. Overall, 45 publications met the inclusion criteria for this review. DNA from whole blood, as well as cell-free DNA (cfDNA) from serum or plasma, was used in these studies. The most common method used for measuring global DNA methylation was the investigation of repetitive elements as surrogates and the application of array-based genome-wide methylation analysis. For measuring gene-specific methylation level, methylation-specific PCR and pyrosequencing were the most frequently used methods. Epigenome-wide blood DNA hypomethylation in BC patients were reported in several studies; however, the evidence is still not conclusive. The most frequently investigated gene in whole blood was BRCA1, which was found more frequently methylated in patients compared to controls. RASSF1A was the most widely investigated gene in cfDNA of serum or plasma, which was also found more frequently methylated in patients compared to controls. Several of the eligible studies reported the associations of global hypomethylation and increased BC risk. Studies investigated associations between gene-specific methylation and BC risk, while got heterogeneous results. But two studies reported that hypermethylation of ATM gene was associated with increased BC risk, which suggest the potential use of this gene for BC risk stratification. Overall, our review suggests the possibility of using blood-based DNA methylation marker as promising marker for BC risk stratification, as several studies found associations between certain methylation level in blood and BC risk. However, so far, the evidence is still quite limited. Optimal markers are yet to be developed and promising results needed to be validated in prospective study cohorts and tested in large screening populations.