Clinical characteristics and HLA associations of azithromycin‐induced liver injury

Alimentary Pharmacology & Therapeutics, Год журнала: 2024, Номер 60(6), С. 787 - 795

Опубликована: Июль 10, 2024

Azithromycin (AZ) is a widely used antibiotic. The aim of this study was to characterise the clinical features, outcomes, and HLA association in patients with drug-induced liver injury (DILI) due AZ.

Язык: Английский

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Association between viral infections and glioma risk: a two-sample bidirectional Mendelian randomization analysis

BMC Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Дек. 5, 2023

Abstract Background Glioma is one of the leading types brain tumor, but few etiologic factors primary glioma have been identified. Previous observational research has shown an association between viral infection and risk. In this study, we used Mendelian randomization (MR) analysis to explore direction magnitude causal relationship glioma. Methods We conducted a two-sample bidirectional MR using genome-wide study (GWAS) data. Summary statistics data were collected from largest meta-analysis GWAS, involving 12,488 cases 18,169 controls. Single-nucleotide polymorphisms (SNPs) associated with exposures as instrumental variables estimate twelve infections corresponding GWAS addition, sensitivity analyses performed. Results After correcting for multiple tests analysis, detected that genetically predicted herpes zoster (caused by Varicella virus (VZV) infection) significantly decreased risk low-grade (LGG) development (OR = 0.85, 95% CI: 0.76–0.96, P 0.01, FDR 0.04). No effects other eleven on reverse causality detected. Conclusions This first studies in field. show robust evidence supporting caused VZV reduces LGG. The findings our advance understanding etiology

Язык: Английский

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Antibodies to varicella-zoster virus and three other herpesviruses and survival in adults with glioma

Neuro-Oncology, Год журнала: 2023, Номер 25(6), С. 1047 - 1057

Опубликована: Янв. 4, 2023

Abstract Background Lifetime exposure to the varicella-zoster virus (VZV) has been consistently inversely associated with glioma risk, however, relationship of VZV survival in adults not investigated. In this study, we analyzed relation their antibody measurements 4 common herpes viral infections, including VZV, measured post-diagnosis. Methods We IgG cytomegalovirus (CMV), simplex 1/2 (HSV), and Epstein-Barr (EBV) collected from 1378 diagnosed between 1991 2010. Blood was obtained a median 3 months after surgery. Associations patient levels overall were estimated using Cox models adjusted for age, sex, self-reported race, surgery type, dexamethasone usage at blood draw, tumor grade. Models stratified by recruitment series meta-analyzed account time-dependent treatment effects. Results seropositivity improved outcomes (Hazard ratio, HR = 0.70, 95% Confidence Interval 0.54–0.90, P .006). Amongst cases who seropositive antibodies, significantly those above 25th percentile continuous reactivity versus below (HR 0.76, 0.66–0.88, .0003). Antibody EBV separately 0.71, 0.53–0.96, .028). positivity 2 other viruses (CMV, HSV) altered survival. Conclusions Low or antibodies are poorer glioma. Differential immune response rather than may explain these findings.

Язык: Английский

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Response to Lehrer and Rheinstein and to Alexiou, Zagorianakou, and Voulgaris

JNCI Journal of the National Cancer Institute, Год журнала: 2025, Номер 117(3), С. 568 - 569

Опубликована: Янв. 2, 2025

Язык: Английский

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Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 14, 2025

Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices relation to glioma survival 3418 cases 8156 controls. We find that increased platelet lymphocyte ratio (PLR) confers an of (odds (OR) = 1.25, p 0.005), especially tumors isocitrate dehydrogenase (IDH) mutations (OR 1.38, 0.007) IDHmut 1p/19q intact (IDHmut-intact OR 1.53, 0.004) tumors. Genetically inferred counts lymphocytes 0.70, neutrophils (IDHmut 0.69, 0.019; IDHmut-intact 0.60, 0.009) show inverse associations risk, which may reflect enhanced immune-surveillance. Considering survival, we observe higher mortality patients (hazard (HR) 1.65, 95% CI: 1.24–2.20), (HR 1.49, 1.13–1.97), eosinophils 1.59, 1.18–2.14). Polygenic scores for traits are also differentially associated 17 immune microenvironment features subtype-specific manner, including signatures related interferon signaling, PD-1 expression, T-cell/Cytotoxic responses. findings highlight immune-mediated susceptibility mechanisms potential disease management implications. aggressive subtype Here, the authors utilise Mendelian Randomisation investigate correlation patients.

Язык: Английский

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Genome-wide polygenic risk scores predict risk of glioma and molecular subtypes

Neuro-Oncology, Год журнала: 2024, Номер 26(10), С. 1933 - 1944

Опубликована: Июнь 25, 2024

Abstract Background Polygenic risk scores (PRS) aggregate the contribution of many variants to provide a personalized genetic susceptibility profile. Since sample sizes glioma genome-wide association studies (GWAS) remain modest, there is need efficiently capture using available data. Methods We applied method based on continuous shrinkage priors (PRS-CS) model joint effects over 1 million common disease and compared this an approach (PRS-CT) that only selects limited set independent reach significance (P < 5 × 10–8). PRS models were trained GWAS stratified by histological (10 346 cases 14 687 controls) molecular subtype (2632 2445 controls), validated in 2 cohorts. Results PRS-CS was generally more predictive than PRS-CT with median increase explained variance (R2) 24% (interquartile range = 11–30%) across subtypes. Improvements pronounced for glioblastoma (GBM), yielding larger odds ratios (OR) per standard deviation (SD) (OR 1.93, P 2.0 10–54 vs. OR 1.83, 9.4 10–50) higher (R2 2.82% R2 2.56%). Individuals 80th percentile distribution had significantly GBM (0.107%) at age 60 those average (0.046%, 2.4 10–12). Lifetime absolute reached 1.18% 0.76% IDH wildtype tumors individuals 95th percentile. augmented classification mutation status when added demographic factors (AUC 0.839 AUC 0.895, PΔAUC 6.8 10–9). Conclusions Genome-wide has potential enhance detection high-risk help distinguish between prognostic

Язык: Английский

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HLA-DQA1 expression is associated with prognosis and predictable with radiomics in breast cancer

Radiation Oncology, Год журнала: 2023, Номер 18(1)

Опубликована: Июль 11, 2023

Abstract Background High HLA-DQA1 expression is associated with a better prognosis in many cancers. However, the association between and of breast cancer noninvasive assessment are still unclear. This study aimed to reveal investigate potential radiomics predict cancer. Methods In this retrospective study, transcriptome sequencing data, medical imaging clinical follow-up data were downloaded from TCIA ( https://www.cancerimagingarchive.net/ ) TCGA https://portal.gdc.cancer.gov/ databases. The characteristic differences high group (HHD group) low explored. Gene set enrichment analysis, Kaplan‒Meier survival analysis Cox regression performed. Then, 107 dynamic contrast-enhanced magnetic resonance features extracted, including size, shape texture. Using recursive feature elimination gradient boosting machine, model was established expression. Receiver operating (ROC) curves, precision-recall calibration decision curves used for evaluation. Results HHD had outcomes. differentially expressed genes significantly enriched oxidative phosphorylation (OXPHOS) estrogen response early late signalling pathways. radiomic score (RS) output area under ROC (95% CI), accuracy, sensitivity, specificity, positive predictive value, negative value 0.866 (0.775–0.956), 0.825, 0.939, 0.7, 0.775, 0.913 training 0.780 (0.629–0.931), 0.659, 0.81, 0.5, 0.63, 0.714 validation set, respectively, showing good prediction effect. Conclusions Quantitative as biomarker has predicting

Язык: Английский

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Genome-wide Polygenic Risk Scores Predict Risk of Glioma and Molecular Subtypes

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 11, 2024

ABSTRACT Background Polygenic risk scores (PRS) aggregate the contribution of many variants to provide a personalized genetic susceptibility profile. Since sample sizes glioma genome-wide association studies (GWAS) remain modest, there is need find efficient ways capturing factors using available germline data. Methods We developed novel PRS (PRS-CS) that uses continuous shrinkage priors model joint effects over 1 million polymorphisms on disease and compared it an approach (PRS-CT) selects limited set independent reach significance (P<5×10 -8 ). models were trained GWAS results stratified by histological (10,346 cases, 14,687 controls) molecular subtype (2,632 2,445 controls), validated in two cohorts. Results PRS-CS was consistently more predictive than PRS-CT across subtypes with average increase explained variance (R 2 ) 21%. Improvements particularly pronounced for glioblastoma tumors, yielding larger effect (odds ratio (OR)=1.93, P=2.0×10 -54 vs. OR=1.83, P=9.4×10 -50 higher =2.82% R =2.56%). Individuals 95 th percentile distribution had 3-fold lifetime absolute IDH mutant (0.63%) wildtype (0.76%) relative individuals PRS. also showed high classification accuracy mutation status among cases (AUC=0.895). Conclusions Our may improve identification high-risk help distinguish between prognostic subtypes, increasing potential clinical utility genetics patient management. IMPORTANCE OF THE STUDY Inherited variation one only few known contribute gliomagenesis. leverage largest collection show correlated genome yields improved prediction risk. improves according status. Additionally, we refined estimates individual highest percentiles confer significant increases Taken together, our findings further evidence genotyping be used as biomarker assessment non-invasive management patients newly diagnosed brain tumors.

Язык: Английский

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Integration of MRI radiomics and germline genetics to predict the IDH mutation status of gliomas

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 17, 2024

ABSTRACT Gliomas are highly fatal and heterogeneous brain tumors. Molecular subtyping is critical for accurate diagnosis prediction of patient outcomes, with isocitrate dehydrogenase ( IDH ) mutations being the most informative tumor feature. currently relies on resected samples, highlighting need non-invasive, preoperative biomarkers. We investigated integration glioma polygenic risk scores (PRS) radiomic features mutation status. The elastic net classifier was trained a panel 256 from MRI scans, germline PRS demographic information 159 cases in Cancer Genome Atlas. Combining radiomics increased area under receiver operating characteristic curve (AUC) distinguishing IDH-wildtype vs. IDH-mutant 0.824 to 0.890 (P ΔAUC =0.0016). Incorporating age at sex further improved (AUC=0.920). Our multimodal also predicted survival. Patients have tumors had significantly lower mortality (hazard ratio (HR)=0.27, 95% CI: 0.14-0.51, P=6.3×10 −5 ), comparable prognostic trajectories observed biopsy-confirmed In conclusion, our study shows that augmenting imaging-based classifiers genetic profiles may help delineate molecular subtypes improve timely, non-invasive clinical assessment patients.

Язык: Английский

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Positive Association Between the Immunogenetic Human Leukocyte Antigen (HLA) Profiles of Multiple Sclerosis and Brain Cancer

Neuroscience Insights, Год журнала: 2023, Номер 18

Опубликована: Янв. 1, 2023

Previous research has documented elevated risk of brain cancer in patients with multiple sclerosis (MS). Separately, human leukocyte antigen (HLA) been implicated protection or susceptibility for both conditions. The aim the current study was to assess a possible role shared immunogenetic influence on MS and cancer. We first identified an profile each condition based covariance between population frequency 127 high-resolution HLA alleles prevalence 14 Continental Western European countries then evaluated correspondence profiles. Also, since individual carries 12 (2 × 6 genes), we estimated at level. found that profiles were highly correlated overall (P < .001) across all genes strongest association observed DRB1, followed by DQB1 HLA-A. These findings overlap are discussed light immune system response viruses other foreign antigens.

Язык: Английский

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