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International Journal of Environmental... Jun 2022Humans continue to be constantly exposed to mycotoxins, mainly through oral exposure (dietary), inhalation, or dermal contact. Recently, it has been of increasing... (Meta-Analysis)
Meta-Analysis Review
Humans continue to be constantly exposed to mycotoxins, mainly through oral exposure (dietary), inhalation, or dermal contact. Recently, it has been of increasing interest to investigate mycotoxin-linked carcinogenicity. This systematic review was conducted to synthesize evidence of the association between mycotoxin-linked mutations and the risk of cancer, to provide an overview of the data linking exposure to different mycotoxins with human cancer risk, and to provide an update on current research on the risk of cancer associated with human exposure to mycotoxins. PRISMA guidelines were used when conducting the systematic review. PubMed, MEDLINE, and CINAHL electronic databases were comprehensively searched to extract the relevant studies published from inception to May 2022. A total of sixteen relevant studies (4907 participants) were identified and included in this review. Of these, twelve studies were from Asia, while four of the studies were conducted in Africa. The overall meta-analysis result found no significant association, although some of the studies confirmed an association between mycotoxin-linked mutations and primary liver cancer risk. Mainly, the experimental studies have shown associations between mycotoxin-linked mutations and cancer risk, and there is a need for researchers to confirm these links in epidemiological studies in order to guide public health policies and interventions.
Topics: Africa; Diet; Food Contamination; Global Health; Humans; Mutation; Mycotoxins; Neoplasms
PubMed: 35805411
DOI: 10.3390/ijerph19137754 -
Archives of Gynecology and Obstetrics Aug 2022In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP).
OBJECTIVE
To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis.
METHODS
Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I-II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05.
RESULTS
Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026).
CONCLUSION
CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.
Topics: Biomarkers, Tumor; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Humans; Mutation; Prognosis; beta Catenin
PubMed: 35034160
DOI: 10.1007/s00404-021-06385-0 -
Journal of Cancer Research and... 2020Development of human genetic and proteomic research has increased the interest in alternative head-and-neck cancer (HNC) detection methods. The aim of this article, the... (Meta-Analysis)
Meta-Analysis
Development of human genetic and proteomic research has increased the interest in alternative head-and-neck cancer (HNC) detection methods. The aim of this article, the second of two-part series, was to review the scientific literature about novel HNC genetic and proteomic biomarkers. A comprehensive review of the current literature was conducted according to the Preferred Reporting Item for Systematic Review and Meta-analyses guidelines by accessing the NCBI PubMed database. Authors conducted the search of articles in English language published from 2004 to 2015. A total of 50 relevant studies were included in the review. Thirty of them concerned proteomic and twenty genetic alterations in HNC. The present systematic review discovered 242 genes and 44 proteins associated with HNC. Due to inconsistent and sparse results, novel biomarkers cannot be firmly established. Prognostic capacity of genetic markers was not evaluated. Proteins (14-3-3γ, extracellular matrix metalloproteinase inducer, and PA28γ) were described as most valuable for prognostic observation of HNC. A strict methodological protocol for molecular studies must be established.
Topics: Biomarkers, Tumor; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Mutation; Prognosis; Proteomics
PubMed: 32719245
DOI: 10.4103/jcrt.JCRT_145_17 -
Asia-Pacific Journal of Ophthalmology... 2016Retinitis pigmentosa is the most common form of hereditary retinal degeneration causing blindness. Great progress has been made in the identification of the causative... (Review)
Review
Retinitis pigmentosa is the most common form of hereditary retinal degeneration causing blindness. Great progress has been made in the identification of the causative genes. Gene diagnosis will soon become an affordable routine clinical test because of the wide application of next-generation sequencing. Gene-based therapy provides hope for curing the disease. Investigation into the molecular pathways from mutation to rod cell death may reveal targets for developing new treatment. Related progress with existing systematic review is briefly summarized so that readers may find the relevant references for in-depth reading. Future trends in the study of retinitis pigmentosa are also discussed.
Topics: Animals; Clinical Trials as Topic; Cone-Rod Dystrophies; Disease Management; Disease Models, Animal; Gene Expression Profiling; Genetic Therapy; High-Throughput Nucleotide Sequencing; Humans; Mutation; Retinal Degeneration; Retinitis Pigmentosa; Stem Cell Transplantation
PubMed: 27488069
DOI: 10.1097/APO.0000000000000227 -
Seizure Apr 2021Dravet Syndrome (DS) is a rare and severe infantile-onset epileptic encephalopathy. DS research focuses mainly on children. We did a systematic review, completed on... (Review)
Review
Dravet Syndrome (DS) is a rare and severe infantile-onset epileptic encephalopathy. DS research focuses mainly on children. We did a systematic review, completed on January 18, 2021, examining the number of clinical DS studies. We show that there are 208 studies on children exclusively, 28 studies on adults exclusively, and 116 studies involving adults and children combined. This 7:1 ratio of children to adult studies exclusively shows the dearth of research that addresses long-term natural history of DS into adulthood. Through this systematic review, we examine the most up-to-date information in DS adults as it pertains to seizures, electroencephalogram, imaging, treatment, motor abnormalities, cognitive and social behavior outcomes, cardiac abnormalities, sleep disturbances, diagnosis in adults, and mortality. Overall, the frequency of seizures increases in the first decade of life and then myoclonic, atypical absences and focal seizures with impaired awareness tend to decrease in frequency or even disappear in adulthood. Adults tend to have a notable reduction in status epilepticus, especially after 30 years of age. Parkinsonian features were seen in patients as young as 19 years old and are more severe in older patients, suggesting a progression of the parkinsonian symptoms. In adulthood, patients continue to present with behavior problems, associated with a lower health-related quality of life. The leading reported cause of death in DS adults is Sudden Unexpected Death in Epilepsy (SUDEP). Further studies in older adults are needed to understand the long-term outcomes of patients with DS.
Topics: Adult; Epilepsies, Myoclonic; Humans; Infant; Mutation; NAV1.1 Voltage-Gated Sodium Channel; Quality of Life; Spasms, Infantile; Young Adult
PubMed: 33677403
DOI: 10.1016/j.seizure.2021.02.025 -
Annals of Oncology : Official Journal... Apr 2015There is an urgent need for biomarkers to help predict prognosis and guide management of esophageal cancer. This review identifies, evaluates and meta-analyses the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
There is an urgent need for biomarkers to help predict prognosis and guide management of esophageal cancer. This review identifies, evaluates and meta-analyses the evidence for reported somatic and germline DNA sequence biomarkers of outcome and stage.
METHODS
A systematic review was carried out of the PubMed, EMBASE and Cochrane databases (20 August 2014), in conjunction with the ASCO Level of Evidence scale for biomarker research. Meta-analyses were carried out for all reported markers associated with outcome measures by more than one study.
RESULTS
Four thousand and four articles were identified, 762 retrieved and 182 studies included. There were 65 reported markers of survival or recurrence 12 (18.5%) were excluded due to multiple comparisons. Following meta-analysis, significant associations were seen for six tumor variants (mutant TP53 and PIK3CA, copy number gain of ERBB2/HER2, CCND1 and FGF3, and chromosomal instability/ploidy) and seven germline polymorphisms: ERCC1 rs3212986, ERCC2 rs1799793, TP53 rs1042522, MDM2 rs2279744, TYMS rs34743033, ABCB1 rs1045642 and MTHFR rs1801133. Twelve germline markers of treatment complications were reported; 10 were excluded. Two tumor and 15 germline markers (11 excluded) of chemo (radio)therapy response were reported. Following meta-analysis, associations were demonstrated for mutant TP53, ERCC1 rs11615 and XRCC1 rs25487. There were 41 tumor/germline reported markers of stage; 27 (65.9%) were excluded.
CONCLUSIONS
Numerous DNA markers of outcome and stage have been reported, yet few are backed by high-quality evidence. Despite this, a small number of variants appear reliable. These merit evaluation in prospective trials, within the context of high-throughput sequencing and gene expression.
Topics: Biomarkers, Tumor; DNA, Neoplasm; Esophageal Neoplasms; Germ-Line Mutation; Humans; Neoplasm Staging; Polymorphism, Single Nucleotide; Prognosis
PubMed: 25214541
DOI: 10.1093/annonc/mdu449 -
Journal of Gastrointestinal and Liver... Mar 2022Several studies have suggested that mutations in MEFV, the gene responsible for familial Mediterranean fever (FMF), are frequently detected in inflammatory bowel disease... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Several studies have suggested that mutations in MEFV, the gene responsible for familial Mediterranean fever (FMF), are frequently detected in inflammatory bowel disease (IBD) patients. We aimed to provide further evidence regarding a potential correlation between MEFV gene mutations and IBD by identifying all relevant studies and analyzing their results.
METHODS
EMBASE, PubMed/MEDLINE, and Google Scholar were used to identify all studies that published until January 2021 and reported MEFV mutation patterns in patients with ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis (IC) with or without a control group. The Newcastle-Ottawa quality assessment scale was used to appraise the quality of the included studies.
RESULTS
Thirteen observational studies, including 937 patients and 977 controls, were analyzed. MEFV mutation rate in IBD patients was 0.238 (95%CI: 0.209-0.270; I 2 =95%); MEFV mutated alleles were more frequent in IBD patients when compared with controls (p=0.03 for UC, p=0.01 for CD and IC). Subgroup analysis indicated that MEFV mutations were increased in patients with IC when compared with UC and CD (I 2 =91%, p<0.001). Patients with extra-intestinal manifestations and pancolitis had 2.57 (95%CI 1.07-6.14; p=0.03) and 2.02 (95%CI: 1.01-4.04, P=0.049) odds ratios to carry MEFV mutant genotypes, respectively. Exon 10 mutations had the most serious impact. No source of heterogeneity was detected.
CONCLUSIONS
MEFV mutations are common in IBD and are linked with the presence of extra-intestinal manifestations and pancolitis. Further research to assess the clinical significance and evolutionary significance of MEFV mutations in IBD patients is warranted.
Topics: Chronic Disease; Colitis, Ulcerative; Crohn Disease; Familial Mediterranean Fever; Humans; Inflammatory Bowel Diseases; Mutation; Pyrin
PubMed: 35306551
DOI: 10.15403/jgld-4070 -
Jornal de Pediatria 2015This review aimed to organize and consolidate the latest knowledge about mutations and genetic polymorphisms related to hereditary thrombophilia and their potential... (Review)
Review
OBJECTIVES
This review aimed to organize and consolidate the latest knowledge about mutations and genetic polymorphisms related to hereditary thrombophilia and their potential association with pediatric stroke and cerebral palsy (CP).
SOURCES
Scientific articles published from 1993 to 2013, written in Portuguese, English, French, and Spanish, were selected and reviewed. The publications were searched in electronic databases, and also in the collections of local libraries. The terms "hereditary thrombophilia", "polymorphisms", "mutation", "pediatric strokes", and "cerebral palsy" were used for the research.
SUMMARY OF THE FINDINGS
The search in databases and in the bibliographic references retrieved 75 articles for inclusion in this review. Studies that investigated hereditary thrombophilias and their associations to CP and arterial and venous pediatric stroke presented contradictory results. The meta-analysis and case-control studies that showed positive results for this association described only slightly increased relative risks and sometimes had questionable conclusions. The association of two or more hereditary thrombophilias, or the association between thrombophilia and other specific clinical risk factors, suggest a higher risk of CP and pediatric stroke than isolated hereditary thrombophilia.
CONCLUSIONS
Larger, multicenter studies should be developed in order to elucidate the role of mutations leading to hereditary thrombophilia and the development of CP and pediatric stroke. The complex and multifactorial etiology of CP and stroke makes this an arduous and difficult task; however, the benefits generated by these studies are immeasurable.
Topics: Case-Control Studies; Cerebral Palsy; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Intracranial Thrombosis; Meta-Analysis as Topic; Mutation; Polymorphism, Genetic; Risk Factors; Stroke; Thrombophilia
PubMed: 25451211
DOI: 10.1016/j.jped.2014.08.004 -
Critical Reviews in Oncology/hematology Jun 2023P53 is one of the most frequently mutated genes in colorectal cancer (CRC). The present study was undertaken to provide a solid estimate of the prognostic value of p53... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
P53 is one of the most frequently mutated genes in colorectal cancer (CRC). The present study was undertaken to provide a solid estimate of the prognostic value of p53 mutations in metastatic CRC patients.
METHODS
This meta-analysis was done in accordance to the Preferred Reporting Item For Systematic Reviews and Meta-Analysis 2020 guidelines. Studies in English published in the last ten years were searched through PubMed and Google Scholar. Final selection criteria were: 1) association with overall survival, 2) presence of Hazard Ratios (HRs) with 95% Confidence Intervals (CIs). The articles were evaluated for quality and risk of bias using the Newcastle-Ottawa Scale and QUIPS tool, respectively. The meta-analysis was conducted with random-effects model according to the Hartung-Knapp-Sidik-Jonkman method and results were depicted in classical Forest plots. Studies heterogeneity was determined by I and Tau statistics. The relationship between p53 mutation and clinic-pathological variables was examined using the χ test.
RESULTS
Nine articles met the eligibility criteria and went to the final analysis. Sample size ranged from 51 to 1043 patients. All studies were retrospective. The Newcastle Ottawa Scale score was > 6 in all studies, QUIPS risk of bias was low in 6, moderate in 3 studies. Only three studies analysed the entire p53 gene coding region. The DNA sequencing technological platforms varied from Sanger to NGS sequencing techniques. The p53 mutational frequencies ranged from 35.0 % to 73.0 %. A strong association (p < 0.0001) emerged between p53 alteration and left-sided CRC. The final pooled HR (p53 mutated vs p53 wild-type tumors) for overall survival was 1.30 (95 % CI: 0.75-2.25) at random-effects model.
CONCLUSIONS
The available evidence does not support a prognostic role for p53 in metastatic CRC patients. Prospective studies, with larger sample sizes and consistent and harmonized methodology, are needed to explore the prognostic role of p53 in metastatic CRC patients.
Topics: Humans; Colonic Neoplasms; Colorectal Neoplasms; Mutation; Prognosis; Prospective Studies; Rectal Neoplasms; Retrospective Studies; Tumor Suppressor Protein p53
PubMed: 37150312
DOI: 10.1016/j.critrevonc.2023.104018 -
Journal of Internal Medicine Mar 2022Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare but fatal microgliopathy. The diagnosis is often delayed due to multifaceted symptoms... (Meta-Analysis)
Meta-Analysis Review
Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare but fatal microgliopathy. The diagnosis is often delayed due to multifaceted symptoms that can mimic several other neurological disorders. Imaging provides diagnostic clues that help identify cases. The objective of this study was to integrate the literature on neuroimaging phenotypes of CSF1R-related leukoencephalopathy. A systematic review and meta-analysis were performed for neuroimaging findings of CSF1R-related leukoencephalopathy via PubMed, Web of Science, and Embase on 25 August 2021. The search included cases with confirmed CSF1R mutations reported under the previous terms hereditary diffuse leukoencephalopathy with spheroids, pigmentary orthochromatic leukodystrophy, and adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. In 78 studies providing neuroimaging data, 195 cases were identified carrying CSF1R mutations in 14 exons and five introns. Women had a statistically significant earlier age of onset (p = 0.041, 40 vs 43 years). Mean delay between symptom onset and neuroimaging was 2.3 years. Main magnetic resonance imaging (MRI) findings were frontoparietal white matter lesions, callosal thinning, and foci of restricted diffusion. The hallmark computed tomography (CT) finding was white matter calcifications. Widespread cerebral hypometabolism and hypoperfusion were reported using positron emission tomography and single-photon emission computed tomography. In conclusion, CSF1R-related leukoencephalopathy is associated with progressive white matter lesions and brain atrophy that can resemble other neurodegenerative/-inflammatory disorders. However, long-lasting diffusion restriction and parenchymal calcifications are more specific findings that can aid the differential diagnosis. Native brain CT and brain MRI (with and without a contrast agent) are recommended with proposed protocols and pictorial examples are provided.
Topics: Brain; Female; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Mutation; Neuroimaging; Phenotype
PubMed: 34875121
DOI: 10.1111/joim.13420