Phenotypic insights into genetic risk factors for immune-related adverse events in cancer immunotherapy
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 phenotyp...
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| Format: | Article |
| Language: | English |
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Springer
2024-11-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03854-8 |
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| author | Haochuan Ma Dili Song Haibo Zhang Taidong Li Xing Jin |
| author_facet | Haochuan Ma Dili Song Haibo Zhang Taidong Li Xing Jin |
| author_sort | Haochuan Ma |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2c2db8429a934ef0b6ef235337c3a3ae |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-2c2db8429a934ef0b6ef235337c3a3ae2025-02-02T12:26:48ZengSpringerCancer Immunology, Immunotherapy1432-08512024-11-0174111110.1007/s00262-024-03854-8Phenotypic insights into genetic risk factors for immune-related adverse events in cancer immunotherapyHaochuan Ma0Dili Song1Haibo Zhang2Taidong Li3Xing Jin4Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese MedicineIntegrated Chinese and Western Treatment of Oncology Department, Central Hospital of Guangdong Provincial NongkenDepartment of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese MedicineIntegrated Chinese and Western Treatment of Oncology Department, Central Hospital of Guangdong Provincial NongkenDepartment of Laboratory Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou UniversityAbstract 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.https://doi.org/10.1007/s00262-024-03854-8PheWASImmune-related adverse eventsMendelian randomizationRisk factorImmunotherapy |
| spellingShingle | Haochuan Ma Dili Song Haibo Zhang Taidong Li Xing Jin Phenotypic insights into genetic risk factors for immune-related adverse events in cancer immunotherapy Cancer Immunology, Immunotherapy PheWAS Immune-related adverse events Mendelian randomization Risk factor Immunotherapy |
| title | Phenotypic insights into genetic risk factors for immune-related adverse events in cancer immunotherapy |
| title_full | Phenotypic insights into genetic risk factors for immune-related adverse events in cancer immunotherapy |
| title_fullStr | Phenotypic insights into genetic risk factors for immune-related adverse events in cancer immunotherapy |
| title_full_unstemmed | Phenotypic insights into genetic risk factors for immune-related adverse events in cancer immunotherapy |
| title_short | Phenotypic insights into genetic risk factors for immune-related adverse events in cancer immunotherapy |
| title_sort | phenotypic insights into genetic risk factors for immune related adverse events in cancer immunotherapy |
| topic | PheWAS Immune-related adverse events Mendelian randomization Risk factor Immunotherapy |
| url | https://doi.org/10.1007/s00262-024-03854-8 |
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