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Frontiers in Allergy 2023Epigenetics facilitates insights on the impact of host environment on the genesis of chronic rhinosinusitis (CRS) through modulations of host gene expression and... (Review)
Review
BACKGROUND
Epigenetics facilitates insights on the impact of host environment on the genesis of chronic rhinosinusitis (CRS) through modulations of host gene expression and activity. Epigenetic mechanisms such as DNA methylation cause reversible but heritable changes in gene expression over generations of progeny, without altering the DNA base-pair sequences. These studies offer a critical understanding of the environment-induced changes that result in host predisposition to disease and may help in developing novel biomarkers and therapeutics. The goal of this systematic review is to summarize the current evidence on epigenetics of CRS with a focus on chronic rhinosinusitis with nasal polyps (CRSwNP) and highlight gaps that merit further research.
METHODS
A systematic review of the English language literature was performed to identify investigations related to epigenetic studies in subjects with CRS.
RESULTS
The review identified 65 studies. These have focused on DNA methylation and non-coding RNAs, with only a few on histone deacetylation, alternative polyadenylation, and chromatin accessibility. Studies include those investigating and changes or both. Studies also include animal models of CRS. Almost all have been conducted in Asia. The genome-wide studies of DNA methylation found differences in global methylation between CRSwNP and controls, while others specifically found significant differences in methylation of the CpG sites of the thymic stromal lymphopoietin (), , and . In addition, DNA methyltransferase inhibitors and histone deacetylase inhibitors were studied as potential therapeutic agents. Majority of the studies investigating non-coding RNAs focused on micro-RNAs (miRNA) and found differences in global expression of miRNA levels. These studies also revealed some previously known as well as novel targets and pathways such as tumor necrosis factor alpha, TGF beta-1, IL-10, , aryl hydrocarbon receptor, PI3K/AKT pathway, mucin secretion, and vascular permeability. Overall, the studies have found a dysregulation in pathways/genes involving inflammation, immune regulation, tissue remodeling, structural proteins, mucin secretion, arachidonic acid metabolism, and transcription.
CONCLUSIONS
Epigenetic studies in CRS subjects suggest that there is likely a major impact of the environment. However, these are association studies and do not directly imply pathogenesis. Longitudinal studies in geographically and racially diverse population cohorts are necessary to quantify genetic vs. environmental risks for CRSwNP and CRS without nasal polyps and assess heritability risk, as well as develop novel biomarkers and therapeutic agents.
PubMed: 37284022
DOI: 10.3389/falgy.2023.1165271 -
Medicine Feb 2023An increasing number of studies have shown the potential diagnostic value of cell-free DNA (cfDNA) as a new biomarker in the management of thyroid cancer (TC); however,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
An increasing number of studies have shown the potential diagnostic value of cell-free DNA (cfDNA) as a new biomarker in the management of thyroid cancer (TC); however, the accuracy of research results is inconsistent. This meta-analysis is the first to synthesize published results and evaluate the application value of circulating cfDNA in the diagnosis of TC.
METHODS
A search strategy was developed according to PICO (P: Patient; I: Intervention; C: Comparison; O: Outcome) principles. We searched 5 databases until October 2022. Original studies that examined cfDNA for the diagnosis of TC and used pathology as the gold standard were included in this meta-analysis. A random-effects model was used to pool the data extracted from individual studies, including the number of patients and the numbers of true positives, false positives, true negatives, and false negatives.
RESULTS
A total of 622 patients with TC, 547 patients with benign thyroid nodules, and 98 healthy individuals were included in 20 studies reported in 14 articles. The types of cfDNA included in the research include specific mutations of cfDNA, methylation of cfDNA, the content of cfDNA, and cfDNA index. After rigorous statistical analysis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 0.76 (95% confidence interval [CI] 0.62-0.85), 0.87 (95% CI 0.78-0.93), 5.08 (95% CI 3.3-10.3), 0.28 (95% CI 0.17-0.46), 21 (95% CI 9-49), and 0.89 (95% CI 0.86-0.91), respectively. The meta-regression results showed that the number of cfDNAs, cfDNA methylation status, and sample size were the sources of heterogeneity in the specificity of the study. A subgroup analysis showed that the quantitative analysis group (cfDNA level) had a higher diagnostic accuracy than that of the qualitative analysis group (cfDNA methylation, mutation, or integrity index), with a sensitivity of 0.84, specificity of 0.89, and area under the curve of 0.91.
CONCLUSIONS
The results of this meta-analysis suggest that cfDNA has value as an adjunct for the diagnosis of TC. Quantitative detection of cfDNA can achieve relatively high diagnostic accuracy. However, due to heterogeneity, the test results based on cfDNA for TC should be interpreted with caution.
Topics: Humans; Cell-Free Nucleic Acids; ROC Curve; Biomarkers, Tumor; Mutation; Thyroid Neoplasms; Sensitivity and Specificity
PubMed: 36800605
DOI: 10.1097/MD.0000000000032928 -
HGG Advances Jan 2023To identify Lynch syndrome (LS) carriers, DNA mismatch repair (MMR) immunohistochemistry (IHC) is performed on colorectal cancers (CRCs). Upon subsequent LS diagnostics,...
To identify Lynch syndrome (LS) carriers, DNA mismatch repair (MMR) immunohistochemistry (IHC) is performed on colorectal cancers (CRCs). Upon subsequent LS diagnostics, MMR deficiency (MMRd) sometimes remains unexplained (UMMRd). Recently, the importance of complete LS diagnostics to explain UMMRd, involving MMR methylation, germline, and somatic analyses, was stressed. To explore why some MMRd CRCs remain unsolved, we performed a systematic review of the literature and mapped patients with UMMRd diagnosed in our center. A systematic literature search was performed in Ovid Medline, Embase, Web of Science, Cochrane CENTRAL, and Google Scholar for articles on UMMRd CRCs after complete LS diagnostics published until December 15, 2021. Additionally, UMMRd CRCs diagnosed in our center since 1993 were mapped. Of 754 identified articles, 17 were included, covering 74 patients with UMMRd. Five CRCs were microsatellite stable. Upon complete diagnostics, 39 patients had single somatic MMR hits, and six an MMR germline variant of unknown significance (VUS). Ten had somatic pathogenic variants (PVs) in , , , and . The remaining 14 patients were the only identifiable cases in the literature without a plausible identified cause of the UMMRd. Of those, nine were suspected to have LS. In our center, complete LS diagnostics in approximately 5,000 CRCs left seven MMRd CRCs unexplained. All had a somatic MMR hit or MMR germline VUS, indicative of a missed second MMR hit. In vitually all patients with UMMRd, complete LS diagnostics suggest MMR gene involvement. Optimizing detection of currently undetectable PVs and VUS interpretation might explain all UMMRd CRCs, considering UMMRd a case closed.
Topics: Humans; Colorectal Neoplasms; Neoplastic Syndromes, Hereditary; Colorectal Neoplasms, Hereditary Nonpolyposis; Brain Neoplasms
PubMed: 36624813
DOI: 10.1016/j.xhgg.2022.100167 -
Sultan Qaboos University Medical Journal Feb 2023This systematic review and meta-analysis aimed to assess the cytotoxic and genotoxic impacts of waterpipe smoking on oral health. The databases MEDLINE, Cochrane Library... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to assess the cytotoxic and genotoxic impacts of waterpipe smoking on oral health. The databases MEDLINE, Cochrane Library and Dimensions were searched to find studies evaluating whether waterpipe smokers exhibited any cytotoxic or genotoxic effects on their oral cells compared to non-smokers, with regard to mouth neoplasms. Particularly, changes in DNA methylation and p53 expression were assessed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted for the systematic review. Review Manager was utilised for statistical analysis with a significance level at <0.05. To assess the grades of the included articles, a risk of bias analysis was summarised. A forest plot, including some of the included articles included, was created regarding the different grades. A total of 20 studies were included in this review. The results showed that waterpipe smoking has cytotoxic and genotoxic effects on oral cells, with a risk difference of 0.16. Although the published articles are few in number, all confirm the devastating effects of waterpipe smoking related to the carcinogenicity. Waterpipe smoking is harmful to oral health. It causes a series of detrimental cellular and genetic modifications such as acanthosis, epithelial dysplasia and hyperparakeratosis. In addition, waterpipe smoke contains several carcinogenic compounds. As it releases many harmful organic compounds, waterpipe smoking increases the incidence of oral cancer.
Topics: Humans; Oral Health; Water Pipe Smoking; Antineoplastic Agents; Mouth Neoplasms; DNA Damage
PubMed: 36865434
DOI: 10.18295/squmj.6.2022.043 -
European Journal of Midwifery 2023Cannabis and its derivatives are becoming increasingly popular in women's preferences during pregnancy in order to relieve nausea. The present study examines cannabis... (Review)
Review
INTRODUCTION
Cannabis and its derivatives are becoming increasingly popular in women's preferences during pregnancy in order to relieve nausea. The present study examines cannabis use during pregnancy and its effects on the fetus, newborn and later childhood.
METHODS
All primary studies were searched in the databases: PubMed, Scopus, Medline during the period June 2019 to August 2020. The keywords used were 'pregnancy', 'pregnant women', 'cannabis', 'marijuana', 'fetus', 'newborn', 'childhood', and combined with 'AND' and 'OR' Boolean operators. Inclusion criteria were: pregnant users of cannabis as the study group and pregnant non-users of cannabis as the control group; the articles could be in English or in Greek. The exclusion criteria were: unpublished studies, reviews, presentations at conferences, and animal studies.
RESULTS
From the systematic review of the literature, the study included 13 primary research studies in which it was found that the children of mother-user faced: disorders in the sleep cycle, memory problems, hyperactivity, increased chances of low birth weight, prematurity with lower Apgar score in the 1st and 5th minutes and hospitalization in an NICU, DNA methylation at the position CpG.32, and modifications in the brain, especially in the amygdala. In addition, girls had more aggressive behavior at the age of 18 months, shorter breastfeeding period, and neonatal death.
CONCLUSIONS
The use of cannabis during the gestation period by the mother, aggravates the physical and mental development of the fetus, the newborn and the later childhood.
PubMed: 37547668
DOI: 10.18332/ejm/168727 -
Clinical Epigenetics Apr 2019Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual differences in their susceptibility to disease and death. Epigenetic mechanisms may play a role in human ageing, and DNA methylation age biomarkers may be good predictors of age-related diseases and mortality risk. The aims of this systematic review were to identify and synthesise the evidence for an association between peripherally measured DNA methylation age and longevity, age-related disease, and mortality risk.
METHODS
A systematic search was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using relevant search terms, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PsychINFO databases were searched to identify articles meeting the inclusion criteria. Studies were assessed for bias using Joanna Briggs Institute critical appraisal checklists. Data was extracted from studies measuring age acceleration as a predictor of age-related diseases, mortality or longevity, and the findings for similar outcomes compared. Using Review Manager 5.3 software, two meta-analyses (one per epigenetic clock) were conducted on studies measuring all-cause mortality.
RESULTS
Twenty-three relevant articles were identified, including a total of 41,607 participants. Four studies focused on ageing and longevity, 11 on age-related disease (cancer, cardiovascular disease, and dementia), and 11 on mortality. There was some, although inconsistent, evidence for an association between increased DNA methylation age and risk of disease. Meta-analyses indicated that each 5-year increase in DNA methylation age was associated an 8 to 15% increased risk of mortality.
CONCLUSION
Due to the small number of studies and heterogeneity in study design and outcomes, the association between DNA methylation age and age-related disease and longevity is inconclusive. Increased epigenetic age was associated with mortality risk, but positive publication bias needs to be considered. Further research is needed to determine the extent to which DNA methylation age can be used as a clinical biomarker.
Topics: Aging; DNA Methylation; Epigenesis, Genetic; Genetic Association Studies; Genetic Markers; Genetic Predisposition to Disease; Humans; Mortality
PubMed: 30975202
DOI: 10.1186/s13148-019-0656-7 -
European Journal of Cancer (Oxford,... Nov 2022Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review,... (Review)
Review
BACKGROUND
Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review, we give an overview of all currently known clinically relevant molecular markers within IDH-mutant astrocytomas grade 2 to 4.
METHODS
A literature search was performed in five electronic databases for English original papers on patient outcome with respect to a molecular marker as determined by DNA/RNA sequencing, micro-arrays, or DNA methylation profiling in IDH-mutant astrocytomas grade 2 to 4. Papers were included if molecular diagnostics were performed on tumour tissue of at least 15 IDH-mutant astrocytoma patients, and if the investigated molecular markers were not limited to the diagnostic markers MGMT, ATRX, TERT, and/or TP53.
RESULTS
The literature search identified 4508 unique articles, published between August 2012 and December 2021, of which ultimately 44 articles were included. Numerous molecular markers from these papers were significantly correlated to patient outcome. The associations between patient outcome and non-canonical IDH mutations, PI3K mutations, high expression of MSH2, high expression of RAD18, homozygous deletion of CDKN2A/B, amplification of PDGFRA, copy number neutral loss of chromosomal arm 17p, loss of chromosomal arm 19q, the G-CIMP-low DNA methylation cluster, high total CNV, and high tumour mutation burden were confirmed in multiple studies.
CONCLUSIONS
Multiple genetic and epigenetic markers are associated with survival in IDH-mutant astrocytoma patients. Commonly affected are the RB signalling pathway, the RTK-PI3K-mTOR signalling pathway, genomic stability markers, and (epigenetic) gene regulation.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; DNA; DNA-Binding Proteins; Homozygote; Humans; Isocitrate Dehydrogenase; Lymphoma, Follicular; MutS Homolog 2 Protein; Mutation; Phosphatidylinositol 3-Kinases; Sequence Deletion; TOR Serine-Threonine Kinases; Ubiquitin-Protein Ligases
PubMed: 36152406
DOI: 10.1016/j.ejca.2022.08.016 -
Journal of Oncology 2022The detection of cell-free DNA (cfDNA) as a part of "liquid biopsy" of prostate cancer (PCa) has been widely explored. However, its diagnostic value for PCa remains... (Review)
Review
OBJECTIVE
The detection of cell-free DNA (cfDNA) as a part of "liquid biopsy" of prostate cancer (PCa) has been widely explored. However, its diagnostic value for PCa remains controversial. Based on the data from the latest literature published in the past decade, the present review was conducted to clarify the diagnostic value of cfDNA in PCa.
METHODS
The related studies were systematically searched in the databases of PubMed, Embase, Web of Science, and Cochrane Library from January 1, 2010 to December 1, 2020. Sensitivity (SEN), specificity (SPE), and other relative parameters were pooled using a random model.
RESULTS
14 eligible studies with 1049 PCa patients and 973 controls were selected based on the inclusion and exclusion criteria. Results demonstrated that cfDNA showed favorable SPE (0.89, 95% CI: 0.79, 0.94) but unsatisfied SEN (0.56, 95% CI: 0.43, 0.68) in the PCa diagnosis. The positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratios (DOR) were 5.1 (95% CI: 3.1, 8.5), 0.49 (95% CI: 0.39, 0.63), and 10 (95% CI: 6, 17), respectively. The summary receiver operating characteristic graph (SROC) with an area under the curve (AUC) of 0.80 (95% CI: 0.76, 0.83) was constructed which indicated favorable diagnostic accuracy for PCa. Results of the subgroup analysis and metaregression analysis reminded "ethnicity" and "methylation" might be sources of heterogeneity. The potential publication bias was not found using Deek's funnel plot asymmetry test ( > 0.05).
CONCLUSIONS
Our meta-analysis illustrated that the cfDNA could undertake a promising role in the PCa diagnosis.
PubMed: 35669243
DOI: 10.1155/2022/1505087 -
International Journal of Inflammation 2019Epigenetic mechanisms have been suggested to play a role in the genetic regulation of pathways related to inflammation. Therefore, we aimed to systematically review... (Review)
Review
Epigenetic mechanisms have been suggested to play a role in the genetic regulation of pathways related to inflammation. Therefore, we aimed to systematically review studies investigating the association between DNA methylation and histone modifications with circulatory inflammation markers in blood. Five bibliographic databases were screened until 21 November of 2017. We included studies conducted on humans that examined the association between epigenetic marks (DNA methylation and/or histone modifications) and a comprehensive list of inflammatory markers. Of the 3,759 identified references, 24 articles were included, involving, 17,399 individuals. There was suggestive evidence for global hypomethylation but better-quality studies in the future have to confirm this. Epigenome-wide association studies (EWAS) (n=7) reported most of the identified differentially methylated genes to be hypomethylated in inflammatory processes. Candidate genes studies reported 18 differentially methylated genes related to several circulatory inflammation markers. There was no overlap in the methylated sites investigated in candidate gene studies and EWAS, except for which was found to be hypomethylated with higher inflammatory markers in both types of studies. The relation between histone modifications and inflammatory markers was assessed by one study only. This review supports an association between epigenetic marks and inflammation, suggesting hypomethylation of the genome. Important gaps in the quality of studies were reported such as inadequate sample size, lack of adjustment for relevant confounders, and failure to replicate the findings. While most of the studies have been focused on C-reactive protein, further efforts should investigate other inflammatory markers.
PubMed: 31205673
DOI: 10.1155/2019/6273680 -
The World Journal of Men's Health Jul 2024The () gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on methylation pattern in spermatozoa of...
PURPOSE
The () gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on methylation pattern in spermatozoa of infertile patients found higher methylation in spermatozoa from infertile patients than fertile controls. To provide an updated and comprehensive systematic review and meta-analysis on the gene methylation pattern in patients with abnormal sperm parameters compared to men with normal parameters.
MATERIALS AND METHODS
This meta-analysis was registered in PROSPERO (CRD42023397056) and performed following the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included.
RESULTS
Of 354 abstracts evaluated for eligibility, only 6 studies were included in the quantitative synthesis, involving a total of 301 patients and 163 controls. Our analysis showed significantly higher levels of gene methylation in patients compared with controls (standard mean difference [SMD] 2.150, 95% confidence interval [CI] 0.377, 3.922; p=0.017), although there was significant heterogeneity between studies (Q-value=239.90, p<0.001; I²=97.91%). No significant evidence of publication bias was found, although one study was sensitive enough to skew the results, leading to a loss of significance (SMD 1.543, 95% CI -0.300, 3.387; p=0.101). In meta-regression analysis, we found that the results were independent of both ages (p=0.6519) and sperm concentration (p=0.2360).
CONCLUSIONS
Sperm DNA methylation may be associated with epigenetic risk in assisted reproductive techniques (ART). The gene could be included in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART.
PubMed: 37853535
DOI: 10.5534/wjmh.230094