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Journal of Affective Disorders Jun 2022In vivo and in vitro studies suggest that inflammation and oxidative damage may contribute to the pathogenesis of major depressive disorder (MDD) and bipolar disorder... (Review)
Review
BACKGROUND
In vivo and in vitro studies suggest that inflammation and oxidative damage may contribute to the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). Imbalance between DNA damage and repair is an emerging research area examining pathophysiological mechanisms of these major mood disorders. This systematic review sought to review DNA repair enzymes, with emphasis on the base excision repair (BER), in mood disorders.
METHODS
We conducted a comprehensive literature search of Ovid MEDLINE® Epub Ahead of Print, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Ovid MEDLINE® Daily, EMBASE (1947), and PsycINFO for studies investigating the alterations in base excision repair in patients with MDD or BD.
RESULTS
A total of 1364 records were identified. 1352 records remained after duplicates were removed. 24 records were selected for full-text screening and a remaining 12 articles were included in the qualitative synthesis. SNPs (single nucleotide polymorphisms) of several BER genes have been shown to be associated with MDD and BD. However, it was difficult to draw conclusions from BER gene expression studies due to conflicting findings and the small number of studies.
LIMITATIONS
All studies were correlational so it was not possible to draw conclusions regarding causality.
CONCLUSION
Future studies comparing DNA repair during the manic or depressive episode to remission will give us a better insight regarding the role of DNA repair in mood disorders. These alterations might be utilized as diagnostic and prognostic biomarkers as well as measuring treatment response.
Topics: Bipolar Disorder; DNA Repair; Depressive Disorder, Major; Humans; Mood Disorders; Polymorphism, Single Nucleotide
PubMed: 35306122
DOI: 10.1016/j.jad.2022.03.033 -
Frontiers in Oncology 2022The variants of DNA repair genes have been widely reported to be associated with cancer risk in the past decades. As were two crucial members of nucleotide excision...
The variants of DNA repair genes have been widely reported to be associated with cancer risk in the past decades. As were two crucial members of nucleotide excision repair pathway, and polymorphisms are linked with susceptibility to multiple cancers, but the conclusions were controversial. In this updated meta-analysis concerned with and single-nucleotide polymorphisms (SNPs), 160 eligible publications were identified, and we exerted the meta-analysis of correlations between 24 variants and 19 types of cancer. Venice criteria and the false-positive report probability were used to evaluate a cumulative evidence of significant associations. We conducted functional annotations for those strong associations using data from the Encyclopedia of DNA Elements (ENCODE) Project. We obtained 11 polymorphisms significantly related to changed susceptibility to 11 cancers ( < 0.05). Strong evidence was assigned to four variant-related cancer risks in Asians ( rs744154 with bladder cancer, rs2296147 with esophageal cancer, rs17655 with laryngeal cancer and uterine cancer, and rs751402 with gastric cancer), moderate to six SNPs with a risk of eight cancers, and weak to nine SNPs with nine cancers. Data from ENCODE and other public databases showed that the loci of these SNPs with strong evidence might fall in putative functional regions. In conclusion, this paper summarizes comprehensive evidence that common variants of and genes are strongly associated with the risk of bladder cancer, esophageal cancer, laryngeal cancer, uterine cancer, and gastric cancer and elucidates the crucial role of the DNA repair genes in the genetic predisposition to human cancers.
PubMed: 36033436
DOI: 10.3389/fonc.2022.951193 -
Molecular Cancer Research : MCR Jun 2021Mucosal melanoma is a rare subtype of melanoma. To date, there has been no comprehensive systematic collation and statistical analysis of the aberrations and aggregated... (Meta-Analysis)
Meta-Analysis
Mucosal melanoma is a rare subtype of melanoma. To date, there has been no comprehensive systematic collation and statistical analysis of the aberrations and aggregated frequency of driver events across multiple studies. Published studies using whole genome, whole exome, targeted gene panel, or individual gene sequencing were identified. Datasets from these studies were collated to summarize mutations, structural variants, and regions of copy-number alteration. Studies using next-generation sequencing were divided into the "main" cohort ( = 173; fresh-frozen samples), "validation" cohort ( = 48; formalin-fixed, paraffin-embedded samples) and a second "validation" cohort comprised 104 tumors sequenced using a targeted panel. Studies assessing mutations in , and were summarized to assess hotspot mutations. Statistical analysis of the main cohort variant data revealed , and as significantly mutated genes. and mutations occurred more commonly in lower anatomy melanomas and in the upper anatomy. , and were commonly affected by chromosomal copy loss, while , and were commonly amplified. Further notable genomic alterations occurring at lower frequencies indicated commonality of signaling networks in tumorigenesis, including MAPK, PI3K, Notch, Wnt/β-catenin, cell cycle, DNA repair, and telomere maintenance pathways. This analysis identified genomic aberrations that provide some insight to the way in which specific pathways may be disrupted. IMPLICATIONS: Our analysis has shown that mucosal melanomas have a diverse range of genomic alterations in several biological pathways. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/6/991/F1.large.jpg.
Topics: Biomarkers, Tumor; DNA Copy Number Variations; Genetic Predisposition to Disease; Genomics; Humans; Melanoma; Mutation; Signal Transduction; Skin Neoplasms; Whole Genome Sequencing
PubMed: 33707307
DOI: 10.1158/1541-7786.MCR-20-0839 -
Pathology, Research and Practice Feb 2023Numerous studies have indicated that the aberrant expression of LINC00963 is extensively present in various human tumors, and that dysregulation of LINC00963 is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Numerous studies have indicated that the aberrant expression of LINC00963 is extensively present in various human tumors, and that dysregulation of LINC00963 is implicated in the initiation and progression of human cancers. In this meta-analysis, data from diverse malignancies were analyzed to determine whether LINC00963 expression levels were associated with clinical prognosis and immune infiltration in pan-cancer.
MATERIALS AND METHODS
The eligible studies were identified from several electronic databases from the inception to July 2022 through systematic research. LINC00963 expression and survival were estimated using pooled odds ratios and hazard ratios with 95% CI. We used the Kaplan-Meier method and COX analysis for survival analysis. In addition, Spearman's correlation analysis was used to uncover any correlation between LINC00963 and microsatellites instability (MSI), tumor mutational burden (TMB), DNA methyltransferases (DNMTs), immune checkpoint biomarkers, and the related genes of mismatch repair (MMR).
RESULTS
Our findings indicated that overexpression of LINC00963 was related to poor overall survival (OS) (HR =1.32, 95% CI, 1.09-1.59, P = 0.004). The TCGA database also found that abnormal expression of LINC00963 was linked to overall survival in various cancers. Moreover, there is an association between LINC00963 expression and MSI, TMB, and MMR in malignancies of various types.
CONCLUSION
The results of this study indicate that LINC00963 may serve as a prognostic biomarker and a therapeutic target for cancer. By using it, cancer diagnoses can be improved, treatment targets discovered, and prognostic questions improved.
Topics: Humans; RNA, Long Noncoding; Neoplasms; Prognosis; Survival Analysis; Biomarkers, Tumor
PubMed: 36696806
DOI: 10.1016/j.prp.2022.154291 -
Association between the XRCC6 polymorphisms and cancer risks: a systematic review and meta-analysis.Medicine Jan 2015A number of studies have been carried out to investigate the association of X-ray repair complementing defective repair in Chinese hamster cells 6 (XRCC6) polymorphisms... (Meta-Analysis)
Meta-Analysis Review
A number of studies have been carried out to investigate the association of X-ray repair complementing defective repair in Chinese hamster cells 6 (XRCC6) polymorphisms and cancer risks, and the results remained inconsistent and inconclusive.To assess the effect of XRCC6 polymorphisms on cancer susceptibility, we conducted a meta-analysis, up to May 23rd 2014, 6267 cases with different types of tumor and 7536 controls from 20 published case-control studies. Summary odds ratios and corresponding 95% confidence intervals for XRCC6 polymorphism and cancer risk were estimated using fixed- or random-effects models when appropriate. Heterogeneity was assessed by chi-squared-based Q-statistic test, and the sources of heterogeneity were explored by subgroup analyses, logistic meta-regression analyses and Galbraith plot. Publication bias was evaluated by Begg funnel plot and Egger test. Sensitivity analyses were also performed.The rs2267437 polymorphism was associated with a significant increase in risks of overall cancers, breast cancer, renal cell carcinoma and hepatocellular carcinoma, and it could increase the cancer risk in Asian population; the rs5751129 polymorphism could increase the cancer risk in overall cancers; the rs132770 polymorphism was associated with the increased renal cell carcinoma risk; furthermore, the rs132793 polymorphism could decrease breast cancer risk and increase risks in "other cancers".Overall, the results provided evidences that the single nucleotide polymorphisms in XRCC6 promoter region might play different roles in various cancers, indicating different cancers have different tumorigenesis mechanisms. Our studies may perhaps supplement for the disease monitoring of cancers in the future, and additional studies to determine the exact molecular mechanism might provide us with interventions to protect the susceptible subgroups.
Topics: Animals; Antigens, Nuclear; Case-Control Studies; DNA-Binding Proteins; Genetic Heterogeneity; Genetic Predisposition to Disease; Humans; Ku Autoantigen; Neoplasms
PubMed: 25569644
DOI: 10.1097/MD.0000000000000283 -
Journal of Receptor and Signal... Apr 2017Mustard gas (e.g. sulfur mustard (SM)) has been used as a chemical agent in several battles and is still a potential worldwide menace. Besides local absorption,... (Review)
Review
CONTEXT
Mustard gas (e.g. sulfur mustard (SM)) has been used as a chemical agent in several battles and is still a potential worldwide menace. Besides local absorption, particularly in the skin, eyes and lungs, systemic spread of the agent also has detrimental effects on gonads, bone marrow and nervous system. Moreover, chronic exposure of SM to respiratory system causes death. Inducing oxidative stress, and disturbing DNA and tissue repair systems, inflammation and cell death signaling pathways have been introduced as molecular mechanisms of the injury.
METHODS
In this systematic review, more than 1200 (2000-2014) articles focusing on gross or molecular pathological reports in the acute phase of the respiratory injury after SM exposure were reviewed, followed by two different layers of gross and molecular pathological data (clinic and laboratory) integrated together in a spatio-temporal order. Role of epithelial, neutrophil and macrophage cells and three signaling pathways of inflammation, oxidative stress and cell death are covered in details.
RESULTS AND CONCLUSION
Our results propose a critical role of interleukin-17 producing cells in acute and chronic inflammatory responses.
Topics: Cell Death; Chemical Warfare Agents; DNA Damage; DNA Repair; Inflammation; Interleukin-17; Mustard Gas; Oxidative Stress; Signal Transduction
PubMed: 27485024
DOI: 10.1080/10799893.2016.1212374 -
Frontiers in Cardiovascular Medicine 2022Myocardial infarction is the leading cause of death and disability worldwide, and the development of new treatments can help reduce the size of myocardial infarction and...
Myocardial infarction is the leading cause of death and disability worldwide, and the development of new treatments can help reduce the size of myocardial infarction and prevent adverse cardiovascular events. Cardiac repair after myocardial infarction can effectively remove necrotic tissue, induce neovascularization, and ultimately replace granulation tissue. Cardiac inflammation is the primary determinant of whether beneficial cardiac repair occurs after myocardial infarction. Immune cells mediate inflammatory responses and play a dual role in injury and protection during cardiac repair. After myocardial infarction, genetic ablation or blocking of anti-inflammatory pathways is often harmful. However, enhancing endogenous anti-inflammatory pathways or blocking endogenous pro-inflammatory pathways may improve cardiac repair after myocardial infarction. A deficiency of neutrophils or monocytes does not improve overall cardiac function after myocardial infarction but worsens it and aggravates cardiac fibrosis. Several factors are critical in regulating inflammatory genes and immune cells' phenotypes, including DNA methylation, histone modifications, and non-coding RNAs. Therefore, strict control and timely suppression of the inflammatory response, finding a balance between inflammatory cells, preventing excessive tissue degradation, and avoiding infarct expansion can effectively reduce the occurrence of adverse cardiovascular events after myocardial infarction. This article reviews the involvement of neutrophils, monocytes, macrophages, and regulatory T cells in cardiac repair after myocardial infarction. After myocardial infarction, neutrophils are the first to be recruited to the damaged site to engulf necrotic cell debris and secrete chemokines that enhance monocyte recruitment. Monocytes then infiltrate the infarct site and differentiate into macrophages and they release proteases and cytokines that are harmful to surviving myocardial cells in the pre-infarct period. As time progresses, apoptotic neutrophils are cleared, the recruitment of anti-inflammatory monocyte subsets, the polarization of macrophages toward the repair phenotype, and infiltration of regulatory T cells, which secrete anti-inflammatory factors that stimulate angiogenesis and granulation tissue formation for cardiac repair. We also explored how epigenetic modifications regulate the phenotype of inflammatory genes and immune cells to promote cardiac repair after myocardial infarction. This paper also elucidates the roles of alarmin S100A8/A9, secreted frizzled-related protein 1, and podoplanin in the inflammatory response and cardiac repair after myocardial infarction.
PubMed: 36698953
DOI: 10.3389/fcvm.2022.1077290 -
International Journal of Molecular... Dec 2021The prevalence of breast cancer in young women (YWBC) has increased alarmingly. Significant efforts are being made to elucidate the biological mechanisms concerning the...
The prevalence of breast cancer in young women (YWBC) has increased alarmingly. Significant efforts are being made to elucidate the biological mechanisms concerning the development, prognosis, and pathological response in early-onset breast cancer (BC) patients. Dysfunctional DNA repair proteins are implied in BC predisposition, progression, and therapy response, underscoring the need for further analyses on DNA repair genes. Public databases of large patient datasets such as METABRIC, TCGA, COSMIC, and cancer cell lines allow the identification of variants in DNA repair genes and possible precision drug candidates. This study aimed at identifying variants and drug candidates that may benefit Latin American (LA) YWBC. We analyzed pathogenic variants in 90 genes involved in DNA repair in public BC datasets from METABRIC, TCGA, COSMIC, CCLE, and COSMIC Cell Lines Project. Results showed that reported DNA repair germline variants in the LA dataset are underrepresented in large databases, in contrast to other populations. Additionally, only six gene repair variants in women under 50 years old from the study population were reported in BC cell lines. Therefore, there is a need for new approaches to study DNA repair variants reported in young women from LA.
Topics: BRCA1 Protein; Breast Neoplasms; DNA Repair; Female; Humans; Latin America; Mutation; Survival Rate; Tumor Suppressor Protein p53
PubMed: 34884835
DOI: 10.3390/ijms222313030 -
European Journal of Obstetrics,... Nov 2017X-ray repair cross-complementing group 1(XRCC1) gene is one of the DNA repair pathway genes playing a vital role in endometriosis risk. Various studies have explored the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE(S)
X-ray repair cross-complementing group 1(XRCC1) gene is one of the DNA repair pathway genes playing a vital role in endometriosis risk. Various studies have explored the association between them, however, the results remained inconsistent. So to confirm the association between XRCC1 Arg399Gln polymorphism and the risk of endometriosis, a meta-analysis was conducted.
STUDY DESIGN
PubMed, Web of Science, Science Director, Cochrane Library, Google Scholar, China National Knowledge Infrastructure (CNKI) and Wanfang Data databases were searched to identify the all relevant studies before Sep. 30, 2016 focusing on the association between XRCC1 Arg399Gln polymorphism and the risk of endometriosis. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated and analyzed by Review Manager 5.2 and Stata 12 to assess the strength of the association. Meanwhile, Begg's test was used to check the publication bias.
RESULTS
The present meta-analysis identified 6 studies with 646 cases and 616 controls. The overall analysis revealed that the AA genotype exhibited a significant association with a decreased risk for endometriosis compared with GG (OR=0.43, 95%CI=0.20-0.94, P=0.03), GA (OR=0.57, 95%CI=0.35-0.95, P=0.03) and GG+GA (OR=0.54, 95%CI=0.31-0.96, P=0.04) respectively. In addition, subgroup analyses based on varied regions indicated that a total comparisons of allelic and various genetic models had statistical significances among Asians (A allele vs. G allele: OR=0.62, 95%CI=0.48-0.81, P=0.0004; AA vs. GG: OR=0.22, 95%CI=0.11-0.46, P<0.0001; AA vs. GA: OR=0.32, 95%CI=0.16-0.63, P=0.001; AA vs. GG+GA: OR=0.28, 95%CI=0.14-0.54, P=0.0002; AA+GA vs. GG: OR=0.28, 95%CI=0.14-0.54, P=0.008) but not among Middle Eastern. The Begg's test did not reveal any obvious publication bias in the present study.
CONCLUSION(S)
Our meta-analysis suggested that Arg399Gln in XRCC1 was associated with endometriosis risk. And especially in Asians, the A allele might be a preventive factor for this disease. Further well-designed researches with larger sample size and various regions are required to validate our conclusion.
Topics: Alleles; Case-Control Studies; Endometriosis; Female; Genetic Heterogeneity; Humans; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Risk Factors; X-ray Repair Cross Complementing Protein 1
PubMed: 28926725
DOI: 10.1016/j.ejogrb.2017.09.011 -
Medicine Dec 2014Genetic polymorphisms of xeroderma pigmentosum group D (XPD) in the nucleotide excision repair pathway may influence cancer susceptibility by affecting the capacity for... (Meta-Analysis)
Meta-Analysis Review
Genetic polymorphisms of xeroderma pigmentosum group D (XPD) in the nucleotide excision repair pathway may influence cancer susceptibility by affecting the capacity for DNA repair. Studies investigating the association between XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma (HCC) risk reported inconsistent results. The aim of this study was to quantitatively summarize the evidence for such an association. Eligible studies were identified by searching electronic databases including PubMed, Embase, Cochrane library, and CBM, Chinese Biomedical Literature Database, for the period up to October 2014. The association of XPD Lys751Gln and Asp312Asn polymorphisms and HCC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Finally, a total of 11 studies with 4322 cases and 4970 controls were included for XPD Lys751Gln polymorphism and 6 studies with 2223 cases and 2441 controls were available for XPD Asp312Asn polymorphism. With respect to XPD Lys751Gln polymorphism, statistically significant increased HCC risk was found when all studies were pooled into the meta-analysis (Gln/Gln vs Lys/Lys: OR = 1.363, 95% CI 1.065-1.744, P = 0.014; Lys/Gln vs Lys/Lys: OR = 1.205, 95% CI 1.099-1.321, P = 0.000; Gln/Gln+Lys/Gln vs Lys/Lys: OR = 1.300, 95% CI 1.141-1.480, P = 0.000). In subgroup analyses by ethnicity, source of control, Hardy-Weinberg equilibrium (HWE) in controls, hepatitis B virus (HBV) infection, and statistically significant increase of HCC risk was found in East Asians, population-based studies, studies consistent with HWE, and HBV-positive subjects, but not in mixed/other populations, hospital-based studies, studies deviating from HWE, and HBV-negative subjects. With respect to XPD Asp312Asn polymorphism, no significant association with HCC risk was found in the overall and subgroup analyses. The results suggest that the XPD Lys751Gln polymorphism contributes to increased HCC susceptibility, especially in East Asian populations. Further, large and well-designed studies are required to validate this association.
Topics: Amino Acid Substitution; Asian People; Carcinoma, Hepatocellular; Genetic Predisposition to Disease; Humans; Liver Neoplasms; Polymorphism, Single Nucleotide; Xeroderma Pigmentosum Group D Protein
PubMed: 25546681
DOI: 10.1097/MD.0000000000000330