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Grant Details

Grant Number: 1R01CA266676-01A1 Interpret this number
Primary Investigator: Francis, Stephen
Organization: University Of California, San Francisco
Project Title: Discovering Infection-Mediated Pathways of Glioma Etiology and Prognosis By Leveraging Multiplex Serology and Immunogenomics
Fiscal Year: 2022


Abstract

PROJECT SUMMARY Gliomas account for 80% of all malignant brain tumors and have an extremely poor prognosis, with a 5-year survival of 5.1%. The etiology of glioma remains poorly understood, with few established modifiable risk factors. Multiple studies have implicated infections in the development of glioma, however the underlying mechanisms and putative causal pathogens remain unclear. In addition to risk, there is also accumulating evidence from studies investigating novel therapeutics suggesting that immune response to infection may be prognostic in glioma patients. Previous epidemiologic studies have investigated a limited number of pathogens using serological assays that only allowed detection. We seek to conduct a large serologic study measuring 41 antigens from all 12 infections previously associated with glioma using assays that provide quantitative measures of antibody response. Our study will include 1000 glioma case-control pairs with extensive clinical and epidemiologic data. In Aim 1 we will estimate the effect of each individual infection on glioma risk and survival and also examine grouped patterns of co-infections. In Aim 2, we will employ innovative long read sequencing technology to detail all polymorphisms in human leukocyte antigen (HLA) class I and II genes in the same set of subjects. Genetic variation in the HLA region plays a pivotal role in regulating immune response to viral challenge and has been previously linked to glioma risk and progression. We will investigate a range of functional HLA polymorphisms, including antigen-presenting classical alleles and amino acid residues, with respect to glioma risk and survival. In Aim 3, we will integrate serological and HLA sequencing data to delineate host genetic mechanisms of immune response to infection and subsequent effects on glioma endpoints. This will allow us to develop comprehensive immunogenomic models for predicting glioma risk and survival. Taken together, the proposed study will contribute new, high-quality data that will significantly advance our understanding of glioma pathogenesis, as well as inform avenues for prevention and improvement of outcomes in glioma patients.



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