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Medicine Aug 2019Previous investigations yielded inconsistent results for the associations between pancreatic cancer (PC) risk and genetic polymorphisms. The study aimed to perform a... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS
Previous investigations yielded inconsistent results for the associations between pancreatic cancer (PC) risk and genetic polymorphisms. The study aimed to perform a systematic review and meta-analysis of studies exploring association of some genetic polymorphisms and PC risk.
METHODS
We systematically searched on PubMed and Web of Science for association of genetic polymorphisms and PC risk published from 1969 to January 2019. We computed the multivariate odd ratio (OR) and 95% confidence intervals (CI), comparing different genetic types.
RESULTS
The present meta-analysis showed significant associations between deoxyribonucleic acid (DNA) repair gene (X-ray repair cross-complementing group 1 (XRCC1) Arg399GIn and Arg194Trp, excision repair cross complementation 1 (ERCC1) rs11615 and rs3212986, ERCC2 rs13181) polymorphisms and PC risk.
CONCLUSIONS
Because of the limited sample size and ethnicity enrolled in the present meta-analysis, further larger scaled studies should be performed to demonstrate the association.
Topics: DNA Glycosylases; DNA Repair; DNA-Binding Proteins; Endonucleases; Genetic Predisposition to Disease; Humans; Pancreatic Neoplasms; Polymorphism, Single Nucleotide; X-ray Repair Cross Complementing Protein 1; Xeroderma Pigmentosum Group D Protein
PubMed: 31393355
DOI: 10.1097/MD.0000000000016541 -
Medicine Jun 2019The grainyhead-like-2 (GRHL2) genetic variants were reported in age-related hearing impairment (ARHI) susceptibility in several case-control studies. However, their... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The grainyhead-like-2 (GRHL2) genetic variants were reported in age-related hearing impairment (ARHI) susceptibility in several case-control studies. However, their conclusions are conflicting; it is difficult to precisely assess the disease risk associated with the variants. Therefore we conduct the meta-analysis to discover the association of GRHL2 polymorphisms and the risk of ARHI.
METHODS
A related literature search was conducted in on-line databases, such as Wanfang database, China National Knowledge Infrastructure (CNKI), EMBASE, Web of Science, and PubMed (updated to August 30, 2018). We use Review Manager 5.0 and Stata SE 12.0 software to reckon the odds radio (OR), 95% confidence interval (CI) and P value in random- or fixed-effects model according to the I2 value in the heterogeneity test.
RESULTS
2762 cases and 2321 controls in 5 articles were provided data to the meta-analysis. The pooled ORs (95% CI) of the rs10955255 polymorphism were 1.26 (1.05-1.50, P = .01), 1.33 (1.07-1.65, P = .01), and 1.32 (1.12-1.55, P = .0007) in the allele, homozygote and recessive model separately. Besides, a significant association was detected between rs1981361 in mixed population and the ARHI risk in the allele, heterozygote, and dominant genetic model respectively. Then subgroup analyses was performed by ethnicity, for rs10955255 meaningful associations were detected for the allele model, homozygote model, dominant model and recessive model in the Caucasian population but no relations in any of the 5 genetic models in Asian population.
CONCLUSION
The meta-analysis indicated that the rs10955255 polymorphism could be an important risk factor for ARHI, especially in the Caucasians. The rs1981361 polymorphism may be a risk factor for ARHI in Asians. Larger scale researches are needed to further bring the consequences up to date.
Topics: Age Factors; Case-Control Studies; DNA-Binding Proteins; Hearing Loss; Humans; Polymorphism, Single Nucleotide; Risk Factors; Transcription Factors
PubMed: 31232964
DOI: 10.1097/MD.0000000000016128 -
Medicine May 2019Excision repair cross-complementation group 1 (ERCC1) protein is a member of the nucleotide excision repair (NER) system, which plays an important role in DNA damage... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Excision repair cross-complementation group 1 (ERCC1) protein is a member of the nucleotide excision repair (NER) system, which plays an important role in DNA damage repair. Recently, its predictive and prognostic value in nasopharyngeal carcinoma (NPC) has been investigated by several studies. However, their results remain controversial.
OBJECTIVES
In an attempt to address this issue, we conducted the present comprehensive meta-analysis.
DATA SOURCES
Studies published until November 2017 were searched. Finally, total 21 literatures involving 22 cohorts and 2921 NPC patients fulfilled the inclusion criteria.
RESULTS
The pooled results showed that high/positive expression of ERCC1 predicted poor objective response rate (ORR) [odds ratio (OR) = 2.83; 95% confidence interval (CI) = 2.11-3.80; P <.001], overall survival (OS) [hazard ratio (HR) = 1.77; 95% CI = 1.48-2.12; P <.001], and disease-free survival (DFS) (HR = 1.60; 95% CI = 1.43-1.79; P <.001) in NPC. Low heterogeneity was detected among these studies (ORR: I = 0.0%, P = .776; DFS: I = 38.7%, P = .148; OS: I = 0.0%; P = .530). The results of sensitivity analyses and publication bias verified the reliability of our findings.
CONCLUSIONS
This study suggested ERCC1 as a potential predictive and prognostic biomarker for the treatment response and survival prognosis of NPC patients.
Topics: Adult; Biomarkers, Tumor; DNA-Binding Proteins; Disease-Free Survival; Endonucleases; Female; Humans; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Prognosis; Proportional Hazards Models; Reproducibility of Results; Treatment Outcome
PubMed: 31124943
DOI: 10.1097/MD.0000000000015641 -
British Journal of Haematology Sep 2019The mechanisms by which patients with RUNX1 familial platelet disorder with propensity to myeloid malignancies (FPDMM) develop myeloid malignancies (MM) are not fully...
The mechanisms by which patients with RUNX1 familial platelet disorder with propensity to myeloid malignancies (FPDMM) develop myeloid malignancies (MM) are not fully understood. We report the results of targeted next-generation sequencing on three patients with RUNX1 FPDMM who developed acute myeloid leukaemia or myelodysplastic syndromes (AML/MDS). DNA samples were collected from bone marrow, peripheral blood and buccal swabs at different time points. One patient had clonal haematopoiesis, represented by an SRSF2 p.P95R variant, prior to his AML diagnosis, when he developed an additional NRAS p.G12D variant. His sister presented to us with MDS, with a TET2 p.S471fs and identical NRAS p.G12D variant. The third patient, from another family, had an additional RUNX1 p.R204X and an NFE2 p.Q139fs variant at AML diagnosis. This constitutes the first report of NFE2 variants in AML without extramedullary disease and NRAS variants in AML/MDS in the setting of FPDMM. A systematic review of the literature including our findings distinguishes two genetic landscapes at AML transformation from FPDMM characterized by either the presence or absence of somatic abnormalities in RUNX1 with or without variants in genes usually associated with MM. Whether clonal haematopoiesis precedes transformation only in patients without somatic abnormalities in RUNX1 needs further confirmation.
Topics: Blood Platelet Disorders; Core Binding Factor Alpha 2 Subunit; Female; Germ-Line Mutation; Humans; Longitudinal Studies; Male; Middle Aged; Myeloproliferative Disorders
PubMed: 31124578
DOI: 10.1111/bjh.15990 -
BMC Medical Genetics May 2019The X-ray repair cross-complementing group 3 (XRCC3) is an efficient component of homologous recombination and is required for the preservation of chromosomal integrity... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The X-ray repair cross-complementing group 3 (XRCC3) is an efficient component of homologous recombination and is required for the preservation of chromosomal integrity in mammalian cells. The association between Thr241Met single-nucleotide polymorphism (SNP) in this gene and susceptibility to breast cancer has been assessed in several studies. Yet, reports are controversial. The present meta-analysis has been designed to identify whether this SNP is associated with susceptibility to breast cancer.
METHODS
We performed a systematic review and meta-analysis for retrieving the case-control studies on the associations between T241 M SNP and the risk of breast cancer. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to verify the association in dominant, recessive, and homozygote inheritance models.
RESULTS
We included 55 studies containing 30,966 sporadic breast cancer cases, 1174 familial breast cancer cases and 32,890 controls in the meta-analysis. In crude analyses, no association was detected between the mentioned SNP and breast cancer risk in recessive, homozygote or dominant models. However, ethnic based analysis showed that in sporadic breast cancer, the SNP was associated with breast cancer risk in Arab populations in homozygous (OR (95% CI) = 3.649 (2.029-6.563), p = 0.0001) and recessive models (OR (95% CI) = 4.092 (1.806-9.271), p = 0.001). The association was significant in Asian population in dominant model (OR (95% CI) = 1.296, p = 0.029). However, the associations was significant in familial breast cancer in mixed ethnic-based subgroup in homozygote and recessive models (OR (95% CI) = 0.451 (0.309-0.659), p = 0.0001, OR (95% CI) = 0.462 (0.298-0.716), p = 0.001 respectively).
CONCLUSIONS
Taken together, our results in a large sample of both sporadic and familial cases of breast cancer showed insignificant role of Thr241Met in the pathogenesis of this type of malignancy. Such results were more conclusive in sporadic cases. In familial cases, future studies are needed to verify our results.
Topics: Breast Neoplasms; DNA-Binding Proteins; Female; Genetic Predisposition to Disease; Homologous Recombination; Humans; Methionine; Polymorphism, Single Nucleotide; Threonine
PubMed: 31077156
DOI: 10.1186/s12881-019-0809-8 -
Bioscience Reports May 2019Association between the xeroderma pigmentosum complementation group F (XPF)rs2276466 located in the excision repair cross complementation group 4 (ERCC4) gene and cancer... (Meta-Analysis)
Meta-Analysis
Association between the xeroderma pigmentosum complementation group F (XPF)rs2276466 located in the excision repair cross complementation group 4 (ERCC4) gene and cancer susceptibility has been widely investigated. However, results thus far have remained controversial. A meta-analysis was performed to identify the impact of this polymorphism on cancer susceptibility. PubMed, Embase and Science-Web databases were searched systematically up to May 20, 2018, to obtain all the records evaluating the association between the rs2276466 polymorphism and the risk of all types of cancers. We used the odds ratio (OR) as a measure of effect, and pooled the data in a Mantel-Haenszel weighed random-effects meta-analysis to provide a summary estimate of the impact of this polymorphism on gastrointestinal cancer, neurogenic cancer and other cancers (breast cancer and SCCHN). All the analyses were carried out in STATA 14.1.11 case-control studies that consisted of 5730 cases and 6756 controls, were eventually included in our meta-analysis. The significant association was observed between the XPFrs2276466 polymorphism and neurogenic cancer susceptibility (recessive model: OR = 1.648, 95% CI = 1.294-2.098, <0.001). Furthermore, no significant impact of this polymorphism was detected on decreased gastrointestinal cancer risk (dominant model: OR = 1.064, 95%CI = 0.961-1.177, = 0.233). The rs2276466 polymorphism might play different roles in carcinogenesis of various cancer types. Current evidence did not suggest that this polymorphism was directly associated with gastrointestinal susceptibility. However, this polymorphism might contribute to increased neurogenic cancer risk. More preclinical and epidemiological studies are still imperative for further evaluation.
Topics: DNA-Binding Proteins; Genetic Predisposition to Disease; Humans; Models, Genetic; Neoplasm Proteins; Neoplasms; Polymorphism, Genetic
PubMed: 31040199
DOI: 10.1042/BSR20181785 -
Frontiers in Immunology 2019A systematic review and meta-analysis of diagnostic biomarkers for noninvasive diagnosis of acute allograft rejection following liver transplantation. Noninvasive... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis of diagnostic biomarkers for noninvasive diagnosis of acute allograft rejection following liver transplantation. Noninvasive blood and urine markers have been widely explored in recent decades for diagnosing acute rejection after liver transplantation. However, none have been translated into routine clinical use so far due to uncertain diagnostic accuracy, and liver biopsy remains the gold standard. Systematic literature searches of Medline, Cochrane and Embase were conducted up to February 2019 to identify studies evaluating the use of noninvasive markers in diagnosing allograft rejection following liver transplantation. Meta-analysis was performed using a random effects model with DerSimonian-Laird weighting and the hierarchical summary receiver operating curve. Of 560 identified studies, 15 studies (1,445 patients) met the inclusion criteria. The following markers were tested: acid labile nitroso-compounds (NOx), serum amyloid A protein, procalcitonin, peripheral blood eosinophil count, peripheral blood T-cell activation and interleukin 2 (IL-2) receptor, guanylate-binding protein-2 mRNA, graft-derived cell-free DNA, pi-glutathione S-transferase, alpha-glutathione S-transferase and serum HLA class I soluble antigens. Only eosinophil count was tested in multiple studies, and they demonstrated high heterogeneity ( = 72% [95% CI: 0.5-0.99]). IL-2 receptor demonstrated the highest sensitivity (89% [95% CI: 0.78-0.96]) and specificity (81% [95% CI: 0.69-0.89]). IL-2 receptor expression demonstrated the highest diagnostic accuracy, while the peripheral eosinophil count was the only marker tested in more than one study. Presently, liver biopsy remains superior to noninvasive diagnostic biomarkers as most studies exhibited inferior designs, hindering possible translation into clinical application.
Topics: Acute Disease; Biomarkers; Biopsy; Diagnostic Errors; Eosinophils; Graft Rejection; Humans; Leukocyte Count; Liver; Liver Transplantation; Receptors, Interleukin-2; Sensitivity and Specificity; Transplantation, Homologous
PubMed: 31031758
DOI: 10.3389/fimmu.2019.00758 -
BMC Cancer Apr 2019The impact of Tet oncogene family member 2 (TET2) mutations on the prognosis of acute myeloid leukemia (AML) is still controversial. A meta analysis is needed in order... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The impact of Tet oncogene family member 2 (TET2) mutations on the prognosis of acute myeloid leukemia (AML) is still controversial. A meta analysis is needed in order to assess the prognostic significance of TET2 mutation in AML.
METHODS
Five databases including PubMed, Cochrane, EMBase, China National Knowledge Internet (CNKI) and Wanfang database were retrieved to search studies that investigated the correlation between TET2 mutations and outcomes of AML patients. Pooled hazard ratios (HRs) and odds ratios (ORs) were used to assess the effects of TET2 mutations.
RESULTS
Sixteen studies were included. TET2 mutation was an unfavorable prognostic factor for overall survival (OS: HR = 1.386; P < 0.001) and event-free survival (EFS: HR = 1.594; P = 0.002) in patients with AML. For patients under 65 years of age, TET2 mutation predicted an inferior OS (HR = 1.310, P = 0.051) and EFS (HR = 1.429, P = 0.027). For patients with intermediate-risk cytogenetics (IR-AML), mutant TET2 had a significant association with adverse OS (HR = 0.474; P < 0.001). For patients with normal cytogenetics (CN-AML), mutant TET2 also conferred adverse OS (HR = 1.425; P < 0.001) and EFS (HR = 1.450, P < 0.001). Further, among patients with CN-AML, mutant TET2 was associated with inferior OS (HR = 2.034, P < 0.001) and EFS (HR = 2.140, P < 0.001) in the ELN favorable-risk subgroup and an inferior EFS (HR = 1.487; P < 0.001) in the ELN intermediate-Isubgroup. With respect to treatment outcome, TET2 mutation predicted a significantly lower rate of complete remission (CR) in cases with ELN favorable-risk cytogenetics (OR = 0.460, P = 0.011).
CONCLUSIONS
TET2 mutation had adverse impacts on survival and treatment response in AML patients and will contribute to risk-stratification, prognosis prediction and therapy guidance.
Topics: Adult; Aged; China; DNA-Binding Proteins; Dioxygenases; Disease-Free Survival; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Prognosis; Proto-Oncogene Proteins; Remission Induction; Treatment Outcome
PubMed: 31023266
DOI: 10.1186/s12885-019-5602-8 -
European Review For Medical and... Oct 2018The association between excision repair cross-complementation (ERCC) gene family (ERCC1 and ERCC2) and osteosarcoma risk was controversial. The aim of this study was to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The association between excision repair cross-complementation (ERCC) gene family (ERCC1 and ERCC2) and osteosarcoma risk was controversial. The aim of this study was to evaluate the association between ERCC1 or ERCC2 and osteosarcoma risk by systematic meta-analysis.
MATERIALS AND METHODS
Relative studies were retrieved from electronic databases without language restriction. The last search was updated on March 2017. Quality assessment was analyzed by the Newcastle-Ottawa Scale (NOS) score, which was recommended by the Agency for Healthcare Research and Quality (AHRQ). Meta-analysis was conducted by R language package (R 3.12).
RESULTS
This meta-analysis was performed based on 4 case-control studies that included 1208 cases and 2448 controls. The ERCC2-rs1799793 AA+AC > CC (OR=1.3428, 95% CI=1.0201; 1.7674) had an effect on the risk of osteosarcoma development, whereas, there were no significant associations among the other ERCC SNPs (ERCC1 rs3212986, ERCC1 rs11615, and ERCC2 rs13181) and osteosarcoma.
CONCLUSIONS
The ERCC2 rs1799793 polymorphism is related to the high risk of osteosarcoma development.
Topics: Bone Neoplasms; Case-Control Studies; DNA-Binding Proteins; Endonucleases; Genetic Predisposition to Disease; Humans; Osteosarcoma; Phenotype; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors; Xeroderma Pigmentosum Group D Protein
PubMed: 30402838
DOI: 10.26355/eurrev_201810_16142 -
BMC Infectious Diseases Aug 2018Psittacosis outbreak investigations require rapid identification of cases in order to trace possible sources and perform public health risk assessments. In recent... (Review)
Review
BACKGROUND
Psittacosis outbreak investigations require rapid identification of cases in order to trace possible sources and perform public health risk assessments. In recent outbreaks in the Netherlands, such investigations were hampered by the non-specificity of laboratory testing methods to identify human Chlamydia psittaci infections.
METHOD
A systematic search of PubMed and Scopus databases of literature published between 01 January, 1986 and 03 July, 2017 was done to find best practices of laboratory-testing methods used in psittacosis outbreaks of two or more human cases. Reference lists of included articles were hand searched to identify additional articles.
RESULTS
Thirty-seven eligible articles were identified, describing 44 human psittacosis outbreaks in 12 countries. Laboratory tests performed were PCR (with various targets), serologic tests (complement binding reactions, ELISA's, immunofluorescence tests and immuno-peroxidase tests) and culture, in various combinations. The literature provided no 'gold standard' laboratory testing strategy to identify recent human C. psittaci infections. In most psittacosis outbreaks, for a considerable number of cases (or tested individuals in an exposed cohort), C. psittaci infection could not be confirmed, nor excluded as causative pathogen. None of the testing strategies was found to be suitable for (nearly) full case finding.
CONCLUSION
PCR enables rapid identification of human psittacosis patients and helps source finding by genotyping but has the disadvantage that sensitivity is high only in the acute phase. In outbreak situations, there is often a time delay and therefore, there is a need for new serologic testing methods next to PCR, with good specificity and sensitivity. Moreover, serum is easier to collect than the preferred diagnostic materials for PCR. A serologic test that can reliably confirm infection status without the necessity of convalescent serum sampling would enhance case finding, source tracing, identification of risk factors and assessment of burden of disease in various settings.
Topics: Animals; Birds; Chlamydophila psittaci; Clinical Laboratory Techniques; DNA, Bacterial; Databases, Factual; Disease Outbreaks; Humans; Polymerase Chain Reaction; Psittacosis
PubMed: 30165831
DOI: 10.1186/s12879-018-3317-0