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PloS One 2014A systematic review and a meta-analysis were carried out in order to summarize the current published studies and to evaluate LINE-1 hypomethylation in blood and other... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
A systematic review and a meta-analysis were carried out in order to summarize the current published studies and to evaluate LINE-1 hypomethylation in blood and other tissues as an epigenetic marker for cancer risk.
METHODS
A systematic literature search in the Medline database, using PubMed, was conducted for epidemiological studies, published before March 2014. The random-effects model was used to estimate weighted mean differences (MDs) with 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by sample type (tissue or blood samples), cancer types, and by assays used to measure global DNA methylation levels. The Cochrane software package Review Manager 5.2 was used.
RESULTS
A total of 19 unique articles on 6107 samples (2554 from cancer patients and 3553 control samples) were included in the meta-analysis. LINE-1 methylation levels were significantly lower in cancer patients than in controls (MD: -6.40, 95% CI: -7.71, -5.09; p<0.001). The significant difference in methylation levels was confirmed in tissue samples (MD -7.55; 95% CI: -9.14, -65.95; p<0.001), but not in blood samples (MD: -0.26, 95% CI: -0.69, 0.17; p = 0.23). LINE-1 methylation levels were significantly lower in colorectal and gastric cancer patients than in controls (MD: -8.33; 95% CI: -10.56, -6.10; p<0.001 and MD: -5.75; 95% CI: -7.75, -3.74; p<0.001) whereas, no significant difference was observed for hepatocellular cancer.
CONCLUSIONS
The present meta-analysis adds new evidence to the growing literature on the role of LINE-1 hypomethylation in human cancer and demonstrates that LINE-1 methylation levels were significantly lower in cancer patients than in control samples, especially in certain cancer types. This result was confirmed in tissue samples, both fresh/frozen or FFPE specimens, but not in blood. Further studies are needed to better clarify the role of LINE-1 methylation in specific subgroups, considering both cancer and sample type, and the methods of measurement.
Topics: Biomarkers, Tumor; DNA Methylation; Epigenesis, Genetic; Humans; Long Interspersed Nucleotide Elements; Neoplasms; Risk
PubMed: 25275447
DOI: 10.1371/journal.pone.0109478 -
Frontiers in Public Health 2021This systematic review aimed to summarize evidence reporting epigenetic and/or neuro-immuno-endocrine embedding of adverse childhood events (ACEs) in children, with a...
This systematic review aimed to summarize evidence reporting epigenetic and/or neuro-immuno-endocrine embedding of adverse childhood events (ACEs) in children, with a particular focus on the short-term biological effect of those experiences. A search was conducted in PsycINFO®, PubMed®, Isi Web of Knowledge and Scopus, until July 2019, to identify papers reporting the short-term biological effects of exposure to ACEs. The search identified 58 studies, that were included in the review. Regarding exposure, the type of ACE more frequently reported was sexual abuse ( = 26), followed by life stressors ( = 20) and physical abuse ( = 19). The majority ( = 17) of studies showed a positive association between ACEs and biomarkers of the immune system. Regarding DNA methylation 18 studies showed more methylation in participants exposed to ACEs. Two studies presented the effect of ACEs on telomere length and showed that exposure was associated with shorter telomere length. Overall the associations observed across studies followed the hypothesis that ACEs are associated with biological risk already at early ages. This is supporting evidence that ACEs appear to get "under the skin" and induce physiological changes and these alterations might be strongly associated with later development of disease.
Topics: Biomarkers; Child; DNA Methylation; Humans; Physical Abuse
PubMed: 34490175
DOI: 10.3389/fpubh.2021.649825 -
Breast Cancer Research : BCR Jan 2020In patients with hormone receptor-positive breast cancer, differentiating between patients with a low and a high risk of recurrence is an ongoing challenge. In current...
BACKGROUND
In patients with hormone receptor-positive breast cancer, differentiating between patients with a low and a high risk of recurrence is an ongoing challenge. In current practice, prognostic clinical parameters are used for risk prediction. DNA methylation markers have been proven to be of additional prognostic value in several cancer types. Numerous prognostic DNA methylation markers for breast cancer have been published in the literature. However, to date, none of these markers are used in clinical practice.
METHODS
We conducted a systematic review of PubMed and EMBASE to assess the number and level of evidence of published DNA methylation markers for hormone receptor-positive breast cancer. To obtain an overview of the reporting quality of the included studies, all were scored according to the REMARK criteria that were established as reporting guidelines for prognostic biomarker studies.
RESULTS
A total of 74 studies were identified reporting on 87 different DNA methylation markers. Assessment of the REMARK criteria showed variation in reporting quality of the studies. Eighteen single markers and one marker panel were studied in multiple independent populations. Hypermethylation of the markers RASSF1, BRCA, PITX2, CDH1, RARB, PCDH10 and PGR, and the marker panel GSTP1, RASSF1 and RARB showed a statistically significant correlation with poor disease outcome that was confirmed in at least one other, independent study.
CONCLUSION
This systematic review provides an overview on published prognostic DNA methylation markers for hormone receptor-positive breast cancer and identifies eight markers that have been independently validated. Analysis of the reporting quality of included studies suggests that future research on this topic would benefit from standardised reporting guidelines.
Topics: Antigens, CD; BRCA1 Protein; Biomarkers, Tumor; Breast Neoplasms; Cadherins; DNA Methylation; Estrogen Receptor alpha; Female; Glutathione S-Transferase pi; Homeodomain Proteins; Humans; Intracellular Signaling Peptides and Proteins; Neoplasm Recurrence, Local; Nuclear Proteins; Prognosis; Protocadherins; Receptors, Progesterone; Receptors, Retinoic Acid; Transcription Factors; Tumor Suppressor Proteins; Homeobox Protein PITX2
PubMed: 32005275
DOI: 10.1186/s13058-020-1250-9 -
Drug Design, Development and Therapy 2016Lung cancer is the leading cause of cancer-related mortality in men worldwide. Aberrant RARβ promoter methylation has been frequently investigated in non-small-cell... (Meta-Analysis)
Meta-Analysis Review
Lung cancer is the leading cause of cancer-related mortality in men worldwide. Aberrant RARβ promoter methylation has been frequently investigated in non-small-cell lung carcinoma (NSCLC), the most common form of lung cancer. The aim of present study was to carry out a meta-analysis and a systematic review to evaluate clinicopathological significance of RARβ promoter hypermethylation in NSCLC. A systematic literature search was carried out. The data were extracted and assessed by two reviewers independently. The Cochrane software Review Manager 5.2 was used to conduct the review. Odds ratios (ORs) with 95% corresponding confidence intervals (CIs) were calculated. A total of 18 relevant articles were available for meta-analysis which included 1,871 participants. The frequency of RARβ hypermethylation was significantly increased in NSCLC than in nonmalignant lung tissue, and the pooled OR was 5.69 (P<0.00001). RARβ hypermethylation was significantly more frequently observed in adenocarcinoma (AC) than in squamous cell carcinoma (SCC), and the pooled OR was 1.47 (P=0.005). Hypermethylation of RARβ gene in NSCLC was 2.46 times higher in smoking than in nonsmoking individuals, and the pooled OR was 2.46 (P=0.0002). RARβ hypermethylation rate was not significantly correlated with stage of the disease and sex. RARβ gene methylation status was not associated with prognosis of patients with NSCLC. In conclusion, RARβ promoter hypermethylation significantly increased in NSCLC than in non-neoplastic lung tissue and is predominant in AC, suggesting that RARβ methylation contributes to the development of NSCLC, especially AC. RARβ gene is a potential novel target for development of personalized therapy in patients with NSCLC, and is promising in restoration of retinoic acid-target gene induction via demethylation of RARβ1' promoter.
Topics: Carcinoma, Non-Small-Cell Lung; DNA Methylation; Humans; Lung Neoplasms; Molecular Targeted Therapy; Promoter Regions, Genetic; Receptors, Retinoic Acid
PubMed: 27103788
DOI: 10.2147/DDDT.S96766 -
Journal of Cancer Research and... Dec 2014To evaluate the association between runt-related transcription factor 3 (RUNX3) gene promoter hypermethylation and gastric cancer risk by meta-analysis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the association between runt-related transcription factor 3 (RUNX3) gene promoter hypermethylation and gastric cancer risk by meta-analysis.
MATERIALS AND METHODS
By searching Medline, EMBASE, Ovid, China National Knowledge Infrastructure and Wanfang databases, the open published articles reporting the relationship between RUNX3 gene promoter hypermethylation, and gastric carcinoma risk, were screened. The aggregated odds ratio of RUNX3 gene promoter hypermethylation in cancerous sample of gastric cancer patients compared to normal gastric tissue of gastric cancer patients was pooled by statistic software STATA-11.0.
RESULTS
Sixteen studies include 2631 samples were finally included in this meta-analysis. The aggregated results indicated that the hypermethylation rate in cancerous tissue was much higher than that in normal tissue (55.1% vs. 26.5%, P < 0.05). And the pooled results showed that the RUNX3 gene promoter methylation odds in tumor tissue in gastric cancer patients compared to normal gastric tissue was 5.47 (95% confidence interval: 3.34-8.96).
CONCLUSION
RUNX3 gene promoter hypermethylation rate was much higher in tumor tissue than that in normal gastric tissue in the patient with gastric cancer.
Topics: Core Binding Factor Alpha 3 Subunit; DNA Methylation; Humans; Promoter Regions, Genetic; Risk Factors; Stomach Neoplasms
PubMed: 25693942
DOI: 10.4103/0973-1482.151539 -
BMC Genetics Jan 2016Increasing evidence suggests the involvement of epigenetic processes in the development of schizophrenia and bipolar disorder, and recent reviews have focused on...
BACKGROUND
Increasing evidence suggests the involvement of epigenetic processes in the development of schizophrenia and bipolar disorder, and recent reviews have focused on findings in post-mortem brain tissue. A systematic review was conducted to synthesise and evaluate the quality of available evidence for epigenetic modifications (specifically DNA methylation) in peripheral blood and saliva samples of schizophrenia and bipolar disorder patients in comparison to healthy controls.
METHODS
Original research articles using humans were identified using electronic databases. There were 33 included studies for which data were extracted and graded in duplicate on 22 items of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement, to assess methodological precision and quality of reporting.
RESULTS
There were 15 genome-wide and 18 exclusive candidate gene loci investigations for DNA methylation studies. A number of common genes were identified as differentially methylated in schizophrenia/bipolar disorder, which were related to reelin, brain-derived neurotrophic factor, dopamine (including the catechol-O-methyltransferase gene), serotonin and glutamate, despite inconsistent findings of hyper-, hypo-, or lack of methylation at these and other loci. The mean STROBE score of 59% suggested moderate quality of available evidence; however, wide methodological variability contributed to a lack of consistency in the way methylation levels were quantified, such that meta-analysis of the results was not possible.
CONCLUSIONS
Moderate quality of available evidence shows some convergence of differential methylation at some common genetic loci in schizophrenia and bipolar disorder, despite wide variation in methodology and reporting across studies. Improvement in the clarity of reporting clinical and other potential confounds would be useful in future studies of epigenetic processes in the context of exposure to environmental and other risk factors.
Topics: Bipolar Disorder; DNA Methylation; Humans; Reelin Protein; Saliva; Schizophrenia
PubMed: 26809779
DOI: 10.1186/s12863-016-0332-2 -
International Journal of Molecular... Mar 2023Cervical intraepithelial neoplasia grade 2 (CIN2) is an intermediate stage between CIN 1, which is a low-grade lesion, and CIN3, which is the immediate precursor of... (Review)
Review
Cervical intraepithelial neoplasia grade 2 (CIN2) is an intermediate stage between CIN 1, which is a low-grade lesion, and CIN3, which is the immediate precursor of cervical cancer (CC). Traditionally, CIN2 was regarded as a high-grade lesion and was treated with conization or ablative methods. In recent years, there has been a shift in the management of younger patients, who are now more often being managed conservatively due to frequent spontaneous CIN2 regression and possible adverse effects of treatment on future pregnancies. Because the risk of progression to CC still exists with conservative management, a personalized approach is needed to identify patients with a higher probability of progression. In this regard, research has focused on the role of host and human papillomavirus (HPV) gene methylation. This systematic review summarizes the current knowledge regarding conservative CIN2 management focusing on the main methylation markers and its implementation in conservative CIN2 management, and it describes major ongoing longitudinal studies on the subject. The review showed that DNA methylation is an accurate predictor of disease progression and a valid triage tool for HPV-positive women, with CIN2 performing better than triage cytology. Because virtually all CCs are methylation-positive, methylation-negative women at baseline have an extremely low risk of CC.
Topics: Pregnancy; Humans; Female; Human Papillomavirus Viruses; Papillomavirus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; DNA Methylation; DNA; Papillomaviridae
PubMed: 37047452
DOI: 10.3390/ijms24076479 -
Psychological Bulletin Sep 2020Life history theory argues that exposure to early life adversity (ELA) accelerates development, although existing evidence for this varies. We present a meta-analysis... (Meta-Analysis)
Meta-Analysis
Life history theory argues that exposure to early life adversity (ELA) accelerates development, although existing evidence for this varies. We present a meta-analysis and systematic review testing the hypothesis that ELA involving threat (e.g., violence exposure) will be associated with accelerated biological aging across multiple metrics, whereas exposure to deprivation (e.g., neglect, institutional rearing) and low-socioeconomic status (SES) will not. We meta-analyze 54 studies ( = 116,010) examining associations of ELA with pubertal timing and cellular aging (telomere length and DNA methylation age), systematically review 25 studies ( = 3,253) examining ELA and neural markers of accelerated development (cortical thickness and amygdala-prefrontal cortex functional connectivity) and evaluate whether associations of ELA with biological aging vary according to the nature of adversity experienced. ELA overall was associated with accelerated pubertal timing ( = -0.10) and cellular aging ( = -0.21), but these associations varied by adversity type. Moderator analysis revealed that ELA characterized by threat was associated with accelerated pubertal development ( = -0.26) and accelerated cellular aging ( = -0.43), but deprivation and SES were unrelated to accelerated development. Systematic review revealed associations between ELA and accelerated cortical thinning, with threat-related ELA consistently associated with thinning in ventromedial prefrontal cortex, and deprivation and SES associated with thinning in frontoparietal, default, and visual networks. There was no consistent association of ELA with amygdala-PFC connectivity. These findings suggest specificity in the types of early environmental experiences associated with accelerated biological aging and highlight the importance of evaluating how accelerated aging contributes to health disparities and whether this process can be mitigated through early intervention. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Topics: Adolescent; Adverse Childhood Experiences; Aging; Aging, Premature; Biomarkers; Brain; Cellular Senescence; Child; Child Abuse; DNA Methylation; Food Insecurity; Humans; Psychosocial Deprivation; Puberty; Social Class; Violence
PubMed: 32744840
DOI: 10.1037/bul0000270 -
Biology of Sex Differences Jul 2020Studies have recently examined the role of epigenetic mechanisms in preeclampsia pathophysiology. One commonly examined epigenetic process is DNA methylation. This...
BACKGROUND
Studies have recently examined the role of epigenetic mechanisms in preeclampsia pathophysiology. One commonly examined epigenetic process is DNA methylation. This heritable epigenetic marker is involved in many important cellular functions. The aim of this study was to establish the association between DNA methylation and preeclampsia and to critically appraise the roles of major study characteristics that can significantly impact the association between DNA methylation and preeclampsia.
MAIN BODY
A systematic review was performed by searching PubMed, Web of Science, and EMBASE for original research articles published over time, until May 31, 2019 in English. Eligible studies compared DNA methylation levels in pregnant women with vs. without preeclampsia. Ninety articles were included. Epigenome-wide studies identified hundreds of differentially methylated places/regions in preeclamptic patients. Hypomethylation was the predominant finding in studies analyzing placental tissue (14/19), while hypermethylation was detected in three studies that analyzed maternal white blood cells (3/3). In candidate gene studies, methylation alterations for a number of genes were found to be associated with preeclampsia. A greater number of differentially methylated genes was found when analyzing more severe preeclampsia (70/82), compared to studies analyzing less severe preeclampsia vs. controls (13/27). A high degree of heterogeneity existed among the studies in terms of methodological study characteristics including design (study design, definition of preeclampsia, control group, sample size, confounders), implementation (biological sample, DNA methylation method, purification of DNA extraction, and validation of methylation), analysis (analytical method, batch effect, genotyping, and gene expression), and data presentation (methylation quantification measure, measure of variability, reporting). Based on the results of this review, we provide recommendations for study design and analytical approach for further studies.
CONCLUSIONS
The findings from this review support the role of DNA methylation in the pathophysiology of preeclampsia. Establishing field-wide methodological and analytical standards may increase value and reduce waste, allowing researchers to gain additional insights into the role of DNA methylation in the pathophysiology of preeclampsia.
Topics: DNA Methylation; Epigenesis, Genetic; Female; Genetic Predisposition to Disease; Humans; Pre-Eclampsia; Pregnancy
PubMed: 32631423
DOI: 10.1186/s13293-020-00313-8 -
The Journals of Gerontology. Series A,... Feb 2020DNA methylation (DNAm) algorithms of biological age provide a robust estimate of an individual's chronological age and can predict their risk of age-related disease and... (Meta-Analysis)
Meta-Analysis
DNA methylation (DNAm) algorithms of biological age provide a robust estimate of an individual's chronological age and can predict their risk of age-related disease and mortality. This study reviewed the evidence that environmental, lifestyle and health factors are associated with the Horvath and Hannum epigenetic clocks. A systematic search identified 61 studies. Chronological age was correlated with DNAm age in blood (median .83, range .13-.99). In a meta-analysis body mass index (BMI) was associated with increased DNAm age (Hannum β: 0.07, 95% CI 0.04 to 0.10; Horvath β: 0.06, 95% CI 0.02 to 0.10), but there was no association with smoking (Hannum β: 0.12, 95% CI -0.50 to 0.73; Horvath β:0.18, 95% CI -0.10 to 0.46). DNAm age was positively associated with frailty (three studies, n = 3,093), and education was negatively associated with the Hannum estimate of DNAm age specifically (four studies, n = 13,955). For most other exposures, findings were too inconsistent to draw conclusions. In conclusion, BMI was positively associated with biological aging measured using DNAm, with some evidence that frailty also increased aging. More research is needed to provide conclusive evidence regarding other exposures. This field of research has the potential to provide further insights into how to promote slower biological aging and ultimately prolong healthy life.
Topics: Age Factors; Aging; Body Mass Index; DNA Methylation; Environment; Health Status; Humans; Life Style
PubMed: 31001624
DOI: 10.1093/gerona/glz099