Haochuan Ma, Dili Song, Haibo Zhang, Taidong Li, Xing Jin
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引用次数: 0
Abstract
Background: Immune-related adverse events (irAEs) pose substantial challenges in the realm of cancer immunotherapy, frequently affecting treatment efficacy and patient safety. To address the urgent need for identifying risk factors associated with irAEs, we conducted a comprehensive phenotype-wide Mendelian randomization analysis (MR-PheWAS).
Methods: Utilizing publicly accessible genome-wide association study (GWAS) data, this investigation evaluated the impact of over 5000 exposure variables on susceptibility to irAEs using univariate Mendelian randomization (MR). We categorized these correlations and further explored potential mechanisms by which associated traits might influence irAEs through multivariate MR.
Results: MR-PheWAS identified numerous risk factors for irAEs, encompassing both previously documented and novel associations. Specifically, we identified 105 traits with probable causal relationships to all-grade irAEs and 119 traits with suggestive associations. For high-grade irAEs, we categorized 122 traits as probably associated and 141 as suggestively associated. Notably, multivariate MR analyses uncovered intricate interactions, particularly highlighting how diabetes impacts all-grade irAEs through mediators such as body mass index and sex hormone-binding globulin.
Conclusions: This study has not only identified new risk factors for irAEs but also confirmed several well-established ones. Further investigation is crucial to validate and assess these identified risk factors within clinical trials. A mechanistic understanding of these causal factors is essential for improving the management and prevention of irAEs.
期刊介绍:
Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions.
The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.