Publications by authors named "Margaret Wrensch"
Background: Temozolomide (TMZ) treatment has demonstrated, but variable, impact on glioma prognosis. This study examines associations of survival with DNA repair gene germline polymorphisms among glioma patients who did and did not have TMZ treatment. Identifying genetic markers which sensitize tumor cells to TMZ could personalize therapy and improve outcomes.
View Article and Find Full Text PDFAssociation of immunoglobulin E levels with glioma risk and survival.
J Natl Cancer Inst
October 2024
Background: Previous epidemiologic studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival.
Methods: We conducted a case-control study using participants from the University of California, San Francisco Adult Glioma Study (1997-2010).
Background: Temozolomide (TMZ) treatment has demonstrated, but variable, impact on glioma prognosis. This study examines associations of survival with DNA repair gene germline polymorphisms among glioma patients who did and did not have TMZ treatment. Identifying genetic markers which sensitize tumor cells to TMZ could personalize therapy and improve outcomes.
View Article and Find Full Text PDFBackground: Variations in survival among patients with oligodendroglioma are unexplained by known prognostic factors. To assess the impact of peripheral immune profiles on prognosis, we applied immunomethylomics analyses-DNA methylation of archived whole blood samples, to characterize immune cells.
Methods: We compared the proportions of immune cells from patients with oligodendroglioma to other glioma subtypes and controls.
Article Synopsis
- Polygenic risk scores (PRS) analyze multiple genetic variants to profile individual susceptibility to glioma, highlighting a need for efficient genetic risk assessment due to limited sample sizes in studies.
- The research compared two PRS methods: one incorporating over 1 million variants (PRS-CS) and another limiting to significant variants (PRS-CT), finding PRS-CS more predictive, especially for glioblastoma.
- Overall, PRS-CS significantly increased predictive accuracy and classification of high-risk individuals, suggesting its potential to better identify glioma subtypes and improve risk detection in clinical settings.
Background: Previous epidemiologic studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival.
Methods: We conducted a case-control study using participants from the University of California, San Francisco Adult Glioma Study (1997-2010).
Article Synopsis
- Researchers developed a new polygenic risk score (PRS-CS) that leverages data from over 1 million genetic variants to assess glioma risk more accurately than traditional methods.
- The study found that PRS-CS significantly improved risk prediction across glioma subtypes, particularly for glioblastoma, showing a 21% increase in explained variance compared to an older approach (PRS-CT).
- This scoring method could enhance the clinical identification of high-risk individuals and aid in differentiating glioma subtypes based on genetics, which may be beneficial for patient management.
Article Synopsis
- * A recent analysis of 3,418 glioma cases found that a higher platelet to lymphocyte ratio (PLR) increased glioma risk, particularly in specific tumor subtypes, while higher lymphocyte and neutrophil counts were linked to reduced risk, suggesting a potential role of genetics in immune surveillance.
- * Although certain blood cell traits did not correlate with survival in most glioma cases, increased lymphocyte counts were associated with higher mortality in a specific tumor subtype, revealing new insights into immune mechanisms that could affect glioma treatment and management.
Article Synopsis
- This study examines the genetic factors contributing to the risk of different cancers by analyzing data from 12 genome-wide association studies, involving nearly 910,000 participants.
- Researchers discovered 15 new cancer susceptibility loci and found that some genetic variants are shared between multiple cancer types, despite much of the heritability being specific to individual cancers.
- The findings indicate the importance of using larger sample sizes for more effective cross-cancer analyses, which could unveil additional genetic regions linked to increased cancer risk.
Background: Lifetime exposure to the varicella-zoster virus (VZV) has been consistently inversely associated with glioma risk, however, the relationship of VZV with survival in adults with glioma has not been investigated. In this study, we analyzed the survival of adults with glioma in relation to their antibody measurements to 4 common herpes viral infections, including VZV, measured post-diagnosis.
Methods: We analyzed IgG antibody measurements to VZV, cytomegalovirus (CMV), herpes simplex virus 1/2 (HSV), and Epstein-Barr virus (EBV) collected from 1378 adults with glioma diagnosed between 1991 and 2010.
Purpose: In patients with diffuse low-grade glioma (LGG), the extent of surgical tumor resection (EOR) has a controversial role, in part because a randomized clinical trial with different levels of EOR is not feasible.
Methods: In a 20-year retrospective cohort of 392 patients with IDH-mutant grade 2 glioma, we analyzed the combined effects of volumetric EOR and molecular and clinical factors on overall survival (OS) and progression-free survival by recursive partitioning analysis. The OS results were validated in two external cohorts (n = 365).
Background: Identifying blood-based DNA methylation patterns is a minimally invasive way to detect biomarkers in predicting age, characteristics of certain diseases and conditions, as well as responses to immunotherapies. As microarray platforms continue to evolve and increase the scope of CpGs measured, new discoveries based on the most recent platform version and how they compare to available data from the previous versions of the platform are unknown. The neutrophil dexamethasone methylation index (NDMI 850) is a blood-based DNA methylation biomarker built on the Illumina MethylationEPIC (850K) array that measures epigenetic responses to dexamethasone (DEX), a synthetic glucocorticoid often administered for inflammation.
View Article and Find Full Text PDFArticle Synopsis
- Establishing causal links between genetic variants and cancer risk is complicated, but this study highlights the single-nucleotide polymorphism rs55705857, which significantly increases the risk of low-grade glioma (LGG).
- The research identifies rs55705857 as the causal variant influencing molecular pathways related to LGG, specifically by disrupting OCT2/4 binding within a brain-specific enhancer, leading to greater gene expression.
- Animal experiments show that altering the corresponding mouse gene accelerated tumor development, demonstrating the variant's role in hereditary susceptibility to severe gliomas in approximately 40% of LGG patients.
Assessing individual responses to glucocorticoid drug therapies that compromise immune status and affect survival outcomes in neuro-oncology is a great challenge. Here we introduce a blood-based neutrophil dexamethasone methylation index (NDMI) that provides a measure of the epigenetic response of subjects to dexamethasone. This marker outperforms conventional approaches based on leukocyte composition as a marker of glucocorticoid response.
View Article and Find Full Text PDFArticle Synopsis
- Recent advancements in the understanding of inherited and acquired genetics related to adult diffuse glioma have revealed specific germline variants linked to different tumor subtypes, particularly glioblastoma (GBM) and lower-grade gliomas.
- Genomewide association studies (GWAS) have identified significant associations that help stratify glioma risks, but findings have largely been limited to European populations.
- The study emphasizes the need for more research in diverse populations to ensure that genetic risk models are applicable to various genetic ancestries across the board.
Introduction: Although immunosuppression is a known characteristic of glioma, no previous large studies have reported peripheral blood immune cell profiles prior to patient surgery and chemoradiation. This report describes blood immune cell characteristics and associated variables prior to surgery among typical glioma patients seen at a large University practice.
Methods: We analyzed pre-surgery blood samples from 139 glioma patients diagnosed with a new or recurrent grade II/III glioma (LrGG, n = 64) or new glioblastoma (GBM, n = 75) and 454 control participants without glioma.
Background: Risk of tumors of the breast, ovary, and meninges has been associated with hormonal factors and with one another. Genome-wide association studies (GWAS) identified a meningioma risk locus on 10p12 near previous GWAS hits for breast and ovarian cancers, raising the possibility of genetic pleiotropy.
Methods: We performed imputation-based fine-mapping in three case-control datasets of meningioma (927 cases, 790 controls), female breast cancer (28 108 cases, 22 209 controls), and ovarian cancer (25 509 cases, 40 941 controls).
Article Synopsis
- Glioma is a deadly type of cancer that may be influenced by genetic factors and infections, with recent studies showing mixed evidence on the role of infections in glioma risk.
- Researchers used genetic predictors to examine the association between immune response to specific viral antigens and glioma risk and survival in a large study group of over 3,400 glioma patients and 8,100 controls.
- They found that certain immune responses to viruses, like Epstein-Barr and Merkel cell polyomavirus, were linked to glioma risk and survival outcomes, and they identified a specific HLA allele associated with a reduced risk of glioma, suggesting the potential for antiviral therapies in treatment.
Background: Genomic profiling studies of diffuse gliomas have led to new improved classification schemes that better predict patient outcomes compared to conventional histomorphology alone. One example is the recognition that patients with IDH-wildtype diffuse astrocytic gliomas demonstrating lower-grade histologic features but genomic and/or epigenomic profile characteristic of glioblastoma typically have poor outcomes similar to patients with histologically diagnosed glioblastoma. Here we sought to determine the clinical impact of prospective genomic profiling for these IDH-wildtype diffuse astrocytic gliomas lacking high-grade histologic features but with molecular profile of glioblastoma.
View Article and Find Full Text PDFBackground: Tumor-based classification of human glioma portends patient prognosis, but considerable unexplained survival variability remains. Host factors (eg, age) also strongly influence survival times, partly reflecting a compromised immune system. How blood epigenetic measures of immune characteristics and age augment molecular classifications in glioma survival has not been investigated.
View Article and Find Full Text PDFAlthough many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC).
View Article and Find Full Text PDFGenome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci.
View Article and Find Full Text PDFBackground: Twenty-five germline variants are associated with adult diffuse glioma, and some of these variants have been shown to be associated with particular subtypes of glioma. We hypothesized that additional germline variants could be identified if a genome-wide association study (GWAS) were performed by molecular subtype.
Methods: A total of 1320 glioma cases and 1889 controls were used in the discovery set and 799 glioma cases and 808 controls in the validation set.
Importance: Per the World Health Organization 2016 integrative classification, newly diagnosed glioblastomas are separated into isocitrate dehydrogenase gene 1 or 2 (IDH)-wild-type and IDH-mutant subtypes, with median patient survival of 1.2 and 3.6 years, respectively.
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